{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:19:52Z","timestamp":1783523992450,"version":"3.55.0"},"reference-count":186,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["PI19\/01166"],"award-info":[{"award-number":["PI19\/01166"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["CB16\/12\/00400"],"award-info":[{"award-number":["CB16\/12\/00400"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["FI20\/00116"],"award-info":[{"award-number":["FI20\/00116"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en C\u00e1ncer (CIBERONC) programme","doi-asserted-by":"publisher","award":["PI19\/01166"],"award-info":[{"award-number":["PI19\/01166"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en C\u00e1ncer (CIBERONC) programme","doi-asserted-by":"publisher","award":["CB16\/12\/00400"],"award-info":[{"award-number":["CB16\/12\/00400"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en C\u00e1ncer (CIBERONC) programme","doi-asserted-by":"publisher","award":["FI20\/00116"],"award-info":[{"award-number":["FI20\/00116"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII-FEDER","doi-asserted-by":"publisher","award":["PI19\/01166"],"award-info":[{"award-number":["PI19\/01166"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII-FEDER","doi-asserted-by":"publisher","award":["CB16\/12\/00400"],"award-info":[{"award-number":["CB16\/12\/00400"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII-FEDER","doi-asserted-by":"publisher","award":["FI20\/00116"],"award-info":[{"award-number":["FI20\/00116"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Systemic mastocytosis (SM) is a rare clonal haematopoietic stem cell disease in which activating KIT mutations (most commonly KIT D816V) are present in virtually every (&gt;90%) adult patient at similar frequencies among non-advanced and advanced forms of SM. The KIT D816V mutation is considered the most common pathogenic driver of SM. Acquisition of this mutation early during haematopoiesis may cause multilineage involvement of haematopoiesis by KIT D816V, which has been associated with higher tumour burden and additional mutations in other genes, leading to an increased rate of transformation to advanced SM. Thus, among other mutations, alterations in around 30 genes that are also frequently mutated in other myeloid neoplasms have been reported in SM cases. From these genes, 12 (i.e., ASXL1, CBL, DNMT3A, EZH2, JAK2, KRAS, NRAS, SF3B1, RUNX1, SF3B1, SRSF2, TET2) have been recurrently reported to be mutated in SM. Because of all the above, assessment of multilineage involvement of haematopoiesis by the KIT D816V mutation, in the setting of multi-mutated haematopoiesis as revealed by a limited panel of genes (i.e., ASXL1, CBL, DNMT3A, EZH2, NRAS, RUNX1 and SRSF2) and associated with a poorer patient outcome, has become of great help to identify SM patients at higher risk of disease progression and\/or poor survival who could benefit from closer follow-up and eventually also early cytoreductive treatment.<\/jats:p>","DOI":"10.3390\/cancers14102487","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T11:59:37Z","timestamp":1652875177000},"page":"2487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4169-4294","authenticated-orcid":false,"given":"Oscar","family":"Gonz\u00e1lez-L\u00f3pez","sequence":"first","affiliation":[{"name":"Cancer Research Center (IBMCC, USAL\/CSIC), Department of Medicine, Universidad de Salamanca, Biomedical Research Institute of Salamanca and Spanish Network on Mastocytosis (REMA), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier I.","family":"Mu\u00f1oz-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Cancer Research Center (IBMCC, USAL\/CSIC), Department of Medicine, Universidad de Salamanca, Biomedical Research Institute of Salamanca and Spanish Network on Mastocytosis (REMA), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Cancer Research Center (IBMCC, USAL\/CSIC), Department of Medicine, Universidad de Salamanca, Biomedical Research Institute of Salamanca and Spanish Network on Mastocytosis (REMA), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"\u00c1lvarez-Twose","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast, Virgen del Valle Hospital) and REMA, 45071 Toledo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-1386","authenticated-orcid":false,"given":"Andr\u00e9s C.","family":"Garc\u00eda-Montero","sequence":"additional","affiliation":[{"name":"Cancer Research Center (IBMCC, USAL\/CSIC), Department of Medicine, Universidad de Salamanca, Biomedical Research Institute of Salamanca and Spanish Network on Mastocytosis (REMA), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","article-title":"Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts","volume":"129","author":"Valent","year":"2017","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41375-021-01406-y","article-title":"Refined diagnostic criteria for bone marrow mastocytosis: A proposal of the European competence network on mastocytosis","volume":"36","author":"Zanotti","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e26; author reply e28","DOI":"10.3324\/haematol.2011.040865","article-title":"Indolent systemic mastocytosis without skin involvement vs. isolated bone marrow mastocytosis","volume":"96","author":"Escribano","year":"2011","journal-title":"Haematologica"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jaci.2015.05.008","article-title":"Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis","volume":"137","author":"Morgado","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.jaci.2009.05.003","article-title":"Prognosis in adult indolent systemic mastocytosis: A long-term study of the Spanish Network on Mastocytosis in a series of 145 patients","volume":"124","author":"Escribano","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1158\/0008-5472.CAN-16-2234","article-title":"Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future","volume":"77","author":"Valent","year":"2017","journal-title":"Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e638","DOI":"10.1016\/S2352-3026(19)30166-8","article-title":"International prognostic scoring system for mastocytosis (IPSM): A retrospective cohort study","volume":"6","author":"Sperr","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/ng0396-312","article-title":"Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: Establishment of clonality in a human mast cell neoplasm","volume":"12","author":"Longley","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1182\/blood-2006-04-015545","article-title":"KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: A prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients","volume":"108","author":"Teodosio","year":"2006","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1182\/blood-2013-04-496448","article-title":"Comprehensive mutational profiling in advanced systemic mastocytosis","volume":"122","author":"Schwaab","year":"2013","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/leu.2015.284","article-title":"Additional mutations in SRSF2, ASXL1 and\/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1182\/blood.2018886507","article-title":"Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis","volume":"134","author":"Henriques","year":"2019","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1182\/bloodadvances.2018020628","article-title":"Impact of somatic and germline mutations on the outcome of systemic mastocytosis","volume":"2","author":"Merker","year":"2018","journal-title":"Blood Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1002\/j.1460-2075.1987.tb02655.x","article-title":"Human proto-oncogene c-kit: A new cell surface receptor tyrosine kinase for an unidentified ligand","volume":"6","author":"Yarden","year":"1987","journal-title":"EMBO J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1365-2141.2007.06619.x","article-title":"Recent advances in the understanding of mastocytosis: The role of KIT mutations","volume":"138","author":"Orfao","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1182\/blood.V84.2.408.408","article-title":"Stem cell factor enhances the survival but not the self-renewal of murine hematopoietic long-term repopulating cells","volume":"84","author":"Li","year":"1994","journal-title":"Blood"},{"key":"ref_17","first-page":"4896","article-title":"c-kit protein, a transmembrane kinase: Identification in tissues and characterization","volume":"8","author":"Majumder","year":"1988","journal-title":"Mol. Cell. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112684","DOI":"10.1016\/j.jim.2019.112684","article-title":"Immunophenotypic dissection of normal hematopoiesis","volume":"475","author":"Orfao","year":"2019","journal-title":"J. Immunol. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1189\/jlb.5RU0614-296R","article-title":"The immunophenotype of mast cells and its utility in the diagnostic work-up of systemic mastocytosis","volume":"97","author":"Teodosio","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1385\/IR:34:2:97","article-title":"Development, migration, and survival of mast cells","volume":"34","author":"Okayama","year":"2006","journal-title":"Immunol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1007\/s00018-004-4273-y","article-title":"Kit as a human oncogenic tyrosine kinase","volume":"61","author":"Kitamura","year":"2004","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1182\/blood.V88.3.995.995","article-title":"Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase","volume":"88","author":"Kitayama","year":"1996","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.anai.2021.07.014","article-title":"Pathogenic and diagnostic relevance of KIT in primary mast cell activation disorders","volume":"127","author":"Orfao","year":"2021","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1146\/annurev.med.55.091902.103822","article-title":"Systemic Mastocytosis","volume":"55","author":"Akin","year":"2004","journal-title":"Annu. Rev. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-related clonal hematopoiesis associated with adverse outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12308-009-0023-2","article-title":"Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia","volume":"2","author":"Pullarkat","year":"2009","journal-title":"J. Hematop."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1097\/01.pas.0000138181.89743.7b","article-title":"CD25 indicates the neoplastic phenotype of mast cells: A novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens","volume":"28","author":"Sotlar","year":"2004","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1046\/j.1365-2141.1997.d01-2042.x","article-title":"A new c-kit mutation in a case of aggressive mast cell disease","volume":"96","author":"Pignon","year":"1997","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/ajh.24426","article-title":"Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival","volume":"91","author":"Pardanani","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1111\/j.1365-2133.2012.10816.x","article-title":"N822K c-kit mutation in CD30-positive cutaneous pleomorphic mastocytosis after germ cell tumour of the ovary","volume":"166","author":"Baek","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/ajh.21713","article-title":"Myelomastocytic leukemia versus mast cell leukemia versus systemic mastocytosis associated with acute myeloid leukemia: A diagnostic challenge","volume":"85","author":"Arredondo","year":"2010","journal-title":"Am. J. Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1200\/JCO.19.00640","article-title":"MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis","volume":"37","author":"Jawhar","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1016\/j.jaip.2020.05.005","article-title":"Importance of Adequate Diagnostic Workup for Correct Diagnosis of Advanced Systemic Mastocytosis","volume":"8","author":"Schwaab","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/1096-8652(200012)65:4<307::AID-AJH10>3.0.CO;2-F","article-title":"Mast cell disease associated with acute myeloid leukemia: Detection of a new c-kit mutation Asp816His","volume":"65","author":"Pullarkat","year":"2000","journal-title":"Am. J. Hematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/ajh.10322","article-title":"Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: Analysis of clinicopathologic features and activating c-kit mutations","volume":"73","author":"Pullarkat","year":"2003","journal-title":"Am. J. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/path.2677","article-title":"Variable presence of KITD816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM-AHNMD)","volume":"220","author":"Sotlar","year":"2010","journal-title":"J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1073\/pnas.96.4.1609","article-title":"Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis","volume":"96","author":"Longley","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1136\/jcp.2003.014860","article-title":"Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: A histopathological challenge","volume":"57","author":"Horny","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/j.exphem.2007.08.016","article-title":"The origin of neoplastic mast cells in systemic mastocytosis with AML1\/ETO-positive acute myeloid leukemia","volume":"35","author":"Nagai","year":"2007","journal-title":"Exp. Hematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/bjh.13560","article-title":"Concurrent activating KIT mutations in systemic mastocytosis","volume":"173","author":"Lasho","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/pbc.24250","article-title":"Systemic mastocytosis associated with t(8;21) acute myeloid leukemia in a child: Detection of the D816A mutation of KIT","volume":"59","author":"Yabe","year":"2012","journal-title":"Pediatric Blood Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tsutsumi, M., Miura, H., Inagaki, H., Shinkai, Y., Kato, A., Kato, T., Hamada-Tsutsumi, S., Tanaka, M., Kudo, K., and Yoshikawa, T. (2020). An aggressive systemic mastocytosis preceded by ovarian dysgerminoma. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07653-z"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/sj.bmt.1705245","article-title":"A pilot study of nonmyeloablative allogeneic hematopoietic stem cell transplant for advanced systemic mastocytosis","volume":"37","author":"Nakamura","year":"2006","journal-title":"Bone Marrow Transpl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1158\/1078-0432.CCR-07-4575","article-title":"Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases","volume":"14","author":"Heinrich","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/gcc.22342","article-title":"Shared clonal cytogenetic abnormalities in aberrant mast cells and leukemic myeloid blasts detected by single nucleotide polymorphism microarray-based whole-genome scanning","volume":"55","author":"Frederiksen","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.3324\/haematol.2017.163964","article-title":"The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm","volume":"102","author":"Jawhar","year":"2017","journal-title":"Haematologica"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lanternier, F., Cohen-Akenine, A., Palmerini, F., Feger, F., Yang, Y., Zermati, Y., Bar\u00e8te, S., Sans, B., Baude, C., and Ghez, D. (2008). Phenotypic and Genotypic Characteristics of Mastocytosis According to the Age of Onset. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001906"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00277-014-2207-9","article-title":"Chronic mast cell leukemia (MCL) with KIT S476I: A rare entity defined by leukemic expansion of mature mast cells and absence of organ damage","volume":"94","author":"Valent","year":"2015","journal-title":"Ann. Hematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1600-0609.2012.01761.x","article-title":"Mast cell leukemia: Identification of a new c-Kit mutation, dup(501-502), and response to masitinib, a c-Kit tyrosine kinase inhibitor","volume":"89","author":"Lhermitte","year":"2012","journal-title":"Eur. J. Haematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e3901","DOI":"10.1097\/MD.0000000000003901","article-title":"Mastocytosis among elderly patients: A multicenter retrospective French study on 53 patients","volume":"95","author":"Rouet","year":"2016","journal-title":"Medicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1182\/blood-2011-12-397588","article-title":"In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells","volume":"120","author":"Soucie","year":"2012","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1600-0609.2011.01598.x","article-title":"A case of mast cell leukaemia with exon 9 KIT mutation and good response to imatinib","volume":"86","author":"Mital","year":"2011","journal-title":"Eur. J. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.leukres.2005.08.015","article-title":"A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy","volume":"30","author":"Zhang","year":"2006","journal-title":"Leuk. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1182\/blood-2003-11-3816","article-title":"A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib","volume":"103","author":"Akin","year":"2004","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.leukres.2018.12.010","article-title":"Molecular response to imatinib in KIT F522C-mutated systemic mastocytosis","volume":"77","author":"Broderick","year":"2019","journal-title":"Leuk. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/labinvest.3700524","article-title":"Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation","volume":"87","author":"Nakagomi","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1046\/j.1523-1747.1998.00414.x","article-title":"Identification of Activating c-kit Mutations in Adult-, but not in Childhood-Onset Indolent Mastocytosis: A Possible Explanation for Divergent Clinical Behavior","volume":"111","author":"Henz","year":"1998","journal-title":"J. Investig. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1172\/JCI116761","article-title":"Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product","volume":"92","author":"Furitsu","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1038\/leu.2011.354","article-title":"Mast-cell leukemia exome sequencing reveals a mutation in the IgE mast-cell receptor beta chain and KIT V654A","volume":"26","author":"Spector","year":"2012","journal-title":"Leukemia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1053\/j.gastro.2005.06.060","article-title":"Novel germline mutation of KIT associated with familial gastrointestinal stromal tumors and mastocytosis","volume":"129","author":"Hartmann","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/ced.12225","article-title":"A new germline mutation in KIT associated with diffuse cutaneous mastocytosis in a Chinese family","volume":"39","author":"Wang","year":"2014","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.leukres.2014.07.010","article-title":"Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412","volume":"38","author":"Visconte","year":"2014","journal-title":"Leuk. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"68950","DOI":"10.18632\/oncotarget.10711","article-title":"Imatinib in systemic mastocytosis: A phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature","volume":"8","author":"Matito","year":"2017","journal-title":"Oncotarget"},{"key":"ref_64","first-page":"1115","article-title":"Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant","volume":"1","author":"Frost","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/S0301-472X(03)00112-7","article-title":"Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit","volume":"31","author":"Akin","year":"2003","journal-title":"Exp. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1182\/blood.V99.5.1741","article-title":"The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations","volume":"99","author":"Ma","year":"2002","journal-title":"Blood"},{"key":"ref_67","first-page":"8","article-title":"FLAG-induced remission in a patient with acute mast cell leukemia (MCL) exhibiting t(7;10)(q22;q26) and KIT D816H","volume":"3","author":"Valent","year":"2014","journal-title":"Leuk. Res. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/gcc.22526","article-title":"Incidence and prognostic impact of cytogenetic aberrations in patients with systemic mastocytosis","volume":"57","author":"Naumann","year":"2018","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0145-2126(01)00038-8","article-title":"Diagnostic criteria and classification of mastocytosis: A consensus proposal","volume":"25","author":"Valent","year":"2001","journal-title":"Leuk. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1182\/blood-2002-01-0203","article-title":"Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene","volume":"100","author":"Yavuz","year":"2002","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1159\/000085563","article-title":"Clonality and molecular pathogenesis of mastocytosis","volume":"114","author":"Akin","year":"2005","journal-title":"Acta Haematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.jaci.2005.02.030","article-title":"Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature","volume":"115","author":"Kocabas","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0301-472X(99)00145-9","article-title":"Analysis of the surface expression of c-kit and occurrence of the c-kit Asp816Val activating mutation in T cells, B cells, and myelomonocytic cells in patients with mastocytosis","volume":"28","author":"Akin","year":"2000","journal-title":"Exp. Hematol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1111\/all.13413","article-title":"Characterization of CD34(+) hematopoietic cells in systemic mastocytosis: Potential role in disease dissemination","volume":"73","author":"Mayado","year":"2018","journal-title":"Allergy"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ebiom.2017.11.024","article-title":"Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal","volume":"26","author":"Valent","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S1525-1578(10)60529-6","article-title":"Demonstration that mast cells, T cells, and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis","volume":"6","author":"Taylor","year":"2004","journal-title":"J. Mol. Diagn. JMD"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1182\/blood-2015-07-655100","article-title":"KIT D816V-mutated bone marrow mesenchymal stem cells in indolent systemic mastocytosis are associated with disease progression","volume":"127","author":"Teodosio","year":"2016","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/modpathol.2015.72","article-title":"Detection of the KIT D816V mutation in peripheral blood of systemic mastocytosis: Diagnostic implications","volume":"28","author":"Teodosio","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.jaci.2012.12.674","article-title":"Gene expression profile of highly purified bone marrow mast cells in systemic mastocytosis","volume":"131","author":"Teodosio","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Traina, F., Visconte, V., Jankowska, A.M., Makishima, H., O\u2019Keefe, C.L., Elson, P., Han, Y., Hsieh, F.H., Sekeres, M.A., and Mali, R.S. (2012). Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043090"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Damaj, G., Joris, M., Chandesris, O., Hanssens, K., Soucie, E., Canioni, D., Kolb, B., Durieu, I., Gyan, E., and Livideanu, C. (2014). ASXL1 but not TET2 mutations adversely impact overall survival of patients suffering systemic mastocytosis with associated clonal hematologic non-mast-cell diseases. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085362"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/bjh.13921","article-title":"Concurrent detection of targeted copy number variants and mutations using a myeloid malignancy next generation sequencing panel allows comprehensive genetic analysis using a single testing strategy","volume":"173","author":"Shen","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41375-018-0342-3","article-title":"Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia","volume":"33","author":"Cross","year":"2019","journal-title":"Leukemia"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3324\/haematol.2010.031690","article-title":"Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis","volume":"96","author":"Wilson","year":"2011","journal-title":"Haematologica"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/leu.2015.4","article-title":"Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event","volume":"29","author":"Jawhar","year":"2015","journal-title":"Leukemia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1038\/leu.2012.130","article-title":"Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders","volume":"26","author":"Visconte","year":"2012","journal-title":"Leukemia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"830","DOI":"10.3324\/haematol.2013.095133","article-title":"SRSF2-p95 hotspot mutation is highly associated with advanced forms of mastocytosis and mutations in epigenetic regulator genes","volume":"99","author":"Hanssens","year":"2014","journal-title":"Haematologica"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/leu.2009.37","article-title":"Frequent TET2 mutations in systemic mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA correlates","volume":"23","author":"Tefferi","year":"2009","journal-title":"Leukemia"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1056\/NEJMoa1716614","article-title":"Classification and Personalized Prognosis in Myeloproliferative Neoplasms","volume":"379","author":"Grinfeld","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/bjh.13865","article-title":"ASXL1 and CBL mutations are independently predictive of inferior survival in advanced systemic mastocytosis","volume":"175","author":"Pardanani","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1182\/blood-2013-08-518886","article-title":"Clinical and biological implications of driver mutations in myelodysplastic syndromes","volume":"122","author":"Papaemmanuil","year":"2013","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/leu.2017.181","article-title":"CHIP, ICUS, CCUS and other four-letter words","volume":"31","author":"Bejar","year":"2017","journal-title":"Leukemia"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00251-014-0768-3","article-title":"Evidence for contribution of epigenetic mechanisms in the pathogenesis of systemic mast cell activation disease","volume":"66","author":"Haenisch","year":"2014","journal-title":"Immunogenetics"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/leu.2013.343","article-title":"Epigenetics of myelodysplastic syndromes","volume":"28","author":"Itzykson","year":"2014","journal-title":"Leukemia"},{"key":"ref_95","first-page":"599","article-title":"The role of mutations in epigenetic regulators in myeloid malignancies. Nature reviews","volume":"12","author":"Shih","year":"2012","journal-title":"Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1038\/leu.2016.190","article-title":"Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2\/ASXL1\/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1016\/S2352-3026(20)30400-2","article-title":"Proposed global prognostic score for systemic mastocytosis: A retrospective prognostic modelling study","volume":"8","author":"Zanotti","year":"2021","journal-title":"Lancet Haematol"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/ni.3691","article-title":"Mechanisms and consequences of Jak-STAT signaling in the immune system","volume":"18","author":"Villarino","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Leardini, D., Messelodi, D., Muratore, E., Baccelli, F., Bertuccio, S.N., Anselmi, L., Pession, A., and Masetti, R. (2022). Role of CBL Mutations in Cancer and Non-Malignant Phenotype. Cancers, 14.","DOI":"10.3390\/cancers14030839"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12185-012-1181-z","article-title":"Epigenetic alterations in hematopoietic malignancies","volume":"96","author":"Chung","year":"2012","journal-title":"Int. J. Hematol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41586-019-1534-3","article-title":"The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape","volume":"573","author":"Weinberg","year":"2019","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1182\/blood-2016-10-695940","article-title":"Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms","volume":"129","author":"Vainchenker","year":"2017","journal-title":"Blood"},{"key":"ref_103","first-page":"5","article-title":"The genetics of myelodysplastic syndrome: From clonal haematopoiesis to secondary leukaemia. Nature reviews","volume":"17","author":"Sperling","year":"2017","journal-title":"Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1056\/NEJM199601043340108","article-title":"Transcription-Factor Mutations and Disease","volume":"334","author":"Latchman","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1182\/blood-2011-02-292102","article-title":"New mutations and pathogenesis of myeloproliferative neoplasms","volume":"118","author":"Vainchenker","year":"2011","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1158\/0008-5472.CAN-10-0610","article-title":"Cbl and human myeloid neoplasms: The Cbl oncogene comes of age","volume":"70","author":"Kales","year":"2010","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1182\/blood-2007-01-066076","article-title":"Flt3-dependent transformation by inactivating c-Cbl mutations in AML","volume":"110","author":"Sargin","year":"2007","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1182\/blood-2006-12-061176","article-title":"Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia","volume":"110","author":"Caligiuri","year":"2007","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1158\/1078-0432.CCR-08-1325","article-title":"CBL exon 8\/9 mutants activate the FLT3 pathway and cluster in core binding factor\/11q deletion acute myeloid leukemia\/myelodysplastic syndrome subtypes","volume":"15","author":"Reindl","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6182","DOI":"10.1182\/blood-2008-12-194548","article-title":"Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms","volume":"113","author":"Grand","year":"2009","journal-title":"Blood"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1182\/blood-2009-08-236596","article-title":"Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm","volume":"115","author":"Beer","year":"2010","journal-title":"Blood"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1200\/JCO.2009.23.7503","article-title":"Mutations of e3 ubiquitin ligase cbl family members constitute a novel common pathogenic lesion in myeloid malignancies","volume":"27","author":"Makishima","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Bader, M.S., and Meyer, S.C. (2022). JAK2 in Myeloproliferative Neoplasms: Still a Protagonist. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020160"},{"key":"ref_114","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.hoc.2020.12.002","article-title":"Genetics of Myeloproliferative Neoplasms","volume":"35","author":"Szybinski","year":"2021","journal-title":"Hematol. Oncol. Clin. N Am."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/bjh.17567","article-title":"Clinical and histopathological features of myeloid neoplasms with concurrent Janus kinase 2 (JAK2) V617F and KIT proto-oncogene, receptor tyrosine kinase (KIT) D816V mutations","volume":"194","author":"Naumann","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/modpathol.2011.109","article-title":"KRAS mutant allele-specific imbalance in lung adenocarcinoma","volume":"24","author":"Chiosea","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1038\/modpathol.2013.71","article-title":"KRAS mutant allele-specific imbalance is associated with worse prognosis in pancreatic cancer and progression to undifferentiated carcinoma of the pancreas","volume":"26","author":"Krasinskas","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_119","first-page":"1946","article-title":"Impact of KRAS mutation on outcome of patients with metastatic colorectal cancer","volume":"61","author":"Chang","year":"2014","journal-title":"Hepato Gastroenterol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1182\/bloodadvances.2018026245","article-title":"Mayo alliance prognostic system for mastocytosis: Clinical and hybrid clinical-molecular models","volume":"2","author":"Pardanani","year":"2018","journal-title":"Blood Adv."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.4049\/jimmunol.180.7.4402","article-title":"AML1\/Runx1 Negatively Regulates Quiescent Hematopoietic Stem Cells in Adult Hematopoiesis","volume":"180","author":"Ichikawa","year":"2008","journal-title":"J. Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1182\/blood-2009-06-223982","article-title":"AML1\/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms","volume":"114","author":"Ding","year":"2009","journal-title":"Blood"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1200\/JCO.2010.30.7926","article-title":"RUNX1 mutations in acute myeloid leukemia: Results from a comprehensive genetic and clinical analysis from the AML study group","volume":"29","author":"Gaidzik","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1200\/JCO.2011.40.7379","article-title":"Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes","volume":"30","author":"Bejar","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1182\/blood-2017-01-764423","article-title":"Response and progression on midostaurin in advanced systemic mastocytosis: KIT D816V and other molecular markers","volume":"130","author":"Jawhar","year":"2017","journal-title":"Blood"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/ajh.24273","article-title":"Next generation sequencing of myeloid neoplasms with eosinophilia harboring the FIP1L1-PDGFRA mutation","volume":"91","author":"Pardanani","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/carcin\/bgp220","article-title":"Epigenetics in cancer","volume":"31","author":"Sharma","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ccr.2009.11.020","article-title":"DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia","volume":"17","author":"Figueroa","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Reszka, E., Jablonska, E., Wieczorek, E., Valent, P., Arock, M., Nilsson, G., Nedoszytko, B., and Niedoszytko, M. (2021). Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062964"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e12074","DOI":"10.1002\/clt2.12074","article-title":"DNA methylation profile in patients with indolent systemic mastocytosis","volume":"11","author":"Gorska","year":"2021","journal-title":"Clin. Transl. Allergy"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/bjc.2013.281","article-title":"Functional and cancer genomics of ASXL family members","volume":"109","author":"Katoh","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1111\/j.1365-2141.2009.07697.x","article-title":"Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia","volume":"145","author":"Trouplin","year":"2009","journal-title":"Br. J. Haematol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1038\/leu.2009.141","article-title":"Mutations of ASXL1 gene in myeloproliferative neoplasms","volume":"23","author":"Carbuccia","year":"2009","journal-title":"Leukemia"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3324\/haematol.2012.064048","article-title":"Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia","volume":"98","author":"Kar","year":"2013","journal-title":"Haematologica"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/leu.2010.69","article-title":"Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1","volume":"24","author":"Tefferi","year":"2010","journal-title":"Leukemia"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"16007","DOI":"10.1038\/celldisc.2016.7","article-title":"Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer","volume":"2","author":"Jia","year":"2016","journal-title":"Cell Discov."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/leu.2011.44","article-title":"Recurrent DNMT3A mutations in patients with myelodysplastic syndromes","volume":"25","author":"Walter","year":"2011","journal-title":"Leukemia"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Tie, R., Zhang, T., Fu, H., Wang, L., Wang, Y., He, Y., Wang, B., Zhu, N., Fu, S., and Lai, X. (2014). Association between DNMT3A mutations and prognosis of adults with de novo acute myeloid leukemia: A systematic review and meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093353"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1182\/blood-2010-10-311019","article-title":"Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A","volume":"118","author":"Jankowska","year":"2011","journal-title":"Blood"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1158\/1078-0432.CCR-10-2156","article-title":"Aberrations of EZH2 in Cancer","volume":"17","author":"Chase","year":"2011","journal-title":"Clinical Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ng.621","article-title":"Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders","volume":"42","author":"Ernst","year":"2010","journal-title":"Nat. Genet"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/ng.620","article-title":"Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes","volume":"42","author":"Nikoloski","year":"2010","journal-title":"Nat. Genet"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/nature09303","article-title":"Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification","volume":"466","author":"Ito","year":"2010","journal-title":"Nature"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1242\/dev.070771","article-title":"Tet family proteins and 5-hydroxymethylcytosine in development and disease","volume":"139","author":"Tan","year":"2012","journal-title":"Development"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccr.2011.06.025","article-title":"The role of TET2 in hematologic neoplasms","volume":"20","author":"Holmfeldt","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1056\/NEJMoa0810069","article-title":"Mutation in TET2 in myeloid cancers","volume":"360","author":"Delhommeau","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/978-3-319-29073-7_9","article-title":"Splicing Factor Mutations in Cancer","volume":"907","author":"Bejar","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/365082a0","article-title":"Specific commitment of different pre-mRNAs to splicing by single SR proteins","volume":"365","author":"Fu","year":"1993","journal-title":"Nature"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/emboj.2010.333","article-title":"Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin","volume":"30","author":"Edmond","year":"2011","journal-title":"EMBO J."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature10496","article-title":"Frequent pathway mutations of splicing machinery in myelodysplasia","volume":"478","author":"Yoshida","year":"2011","journal-title":"Nature"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1182\/blood-2012-01-404863","article-title":"SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML)","volume":"120","author":"Meggendorfer","year":"2012","journal-title":"Blood"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1182\/blood-2011-12-399337","article-title":"Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes","volume":"119","author":"Thol","year":"2012","journal-title":"Blood"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.3324\/haematol.2012.075325","article-title":"Spliceosome mutations exhibit specific associations with epigenetic modifiers and proto-oncogenes mutated in myelodysplastic syndrome","volume":"98","author":"Mian","year":"2013","journal-title":"Haematologica"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"a003707","DOI":"10.1101\/cshperspect.a003707","article-title":"Spliceosome structure and function","volume":"3","author":"Will","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1182\/blood-2018-04-843771","article-title":"Impact of spliceosome mutations on RNA splicing in myelodysplasia: Dysregulated genes\/pathways and clinical associations","volume":"132","author":"Pellagatti","year":"2018","journal-title":"Blood"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1182\/blood-2011-09-377275","article-title":"Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic\/myeloproliferative neoplasms","volume":"118","author":"Malcovati","year":"2011","journal-title":"Blood"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/ng.1031","article-title":"Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes","volume":"44","author":"Graubert","year":"2011","journal-title":"Nat. Genet"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1182\/blood-2011-12-395087","article-title":"Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML","volume":"119","author":"Hirabayashi","year":"2012","journal-title":"Blood"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.jaci.2012.04.013","article-title":"Adult-onset systemic mastocytosis in monozygotic twins with KIT D816V and JAK2 V617F mutations","volume":"130","author":"Kristensen","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.1182\/blood-2009-02-205237","article-title":"Systemic mastocytosis in 342 consecutive adults: Survival studies and prognostic factors","volume":"113","author":"Lim","year":"2009","journal-title":"Blood"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ajhg.2020.12.007","article-title":"Genome-wide association study identifies novel susceptibility loci for KIT D816V positive mastocytosis","volume":"108","author":"Galata","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"De Vita, S., Schneider, R.K., Garcia, M., Wood, J., Gavillet, M., Ebert, B.L., Gerbaulet, A., Roers, A., Levine, R.L., and Mullally, A. (2014). Loss of Function of TET2 Cooperates with Constitutively Active KIT in Murine and Human Models of Mastocytosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096209"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1056\/NEJMoa1013343","article-title":"Clinical Effect of Point Mutations in Myelodysplastic Syndromes","volume":"364","author":"Bejar","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jmoldx.2010.10.004","article-title":"Improved detection of the KIT D816V mutation in patients with systemic mastocytosis using a quantitative and highly sensitive real-time qPCR assay","volume":"13","author":"Kristensen","year":"2011","journal-title":"J. Mol. Diagn. JMD"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/ajh.23672","article-title":"Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis","volume":"89","author":"Kristensen","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00277-013-1964-1","article-title":"The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis","volume":"93","author":"Erben","year":"2014","journal-title":"Ann. Hematol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/all.12409","article-title":"The KIT D816V allele burden predicts survival in patients with mastocytosis and correlates with the WHO type of the disease","volume":"69","author":"Hoermann","year":"2014","journal-title":"Allergy"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Hoermann, G., Sotlar, K., Jawhar, M., Kristensen, T., Bachelot, G., Nedoszytko, B., Carter, M.C., Horny, H.P., Bonadonna, P., and Sperr, W.R. (2022). Standards of Genetic Testing in the Diagnosis and Prognostication of Systemic Mastocytosis in 2022: Recommendations of the EU-US Cooperative Group. J. Allergy Clin. Immunol. Pract.","DOI":"10.1016\/j.jaip.2022.03.001"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1182\/blood-2015-03-631747","article-title":"Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes","volume":"126","author":"Steensma","year":"2015","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1182\/blood-2017-02-769869","article-title":"Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly","volume":"130","author":"Zink","year":"2017","journal-title":"Blood"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/ng.2270","article-title":"Detectable clonal mosaicism and its relationship to aging and cancer","volume":"44","author":"Jacobs","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ng.2271","article-title":"Detectable clonal mosaicism from birth to old age and its relationship to cancer","volume":"44","author":"Laurie","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1182\/blood.V124.21.3272.3272","article-title":"Somatic Mutations Indicative of Clonal Hematopoiesis Are Present in a Large Fraction of Cytopenic Patients Who Lack Diagnostic Evidence of MDS","volume":"124","author":"Hall","year":"2014","journal-title":"Blood"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1182\/blood-2017-07-746453","article-title":"Age-related clonal hematopoiesis","volume":"131","author":"Shlush","year":"2018","journal-title":"Blood"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Valent, P., Kern, W., Hoermann, G., Milosevic Feenstra, J.D., Sotlar, K., Pfeilst\u00f6cker, M., Germing, U., Sperr, W.R., Reiter, A., and Wolf, D. (2019). Clonal Hematopoiesis with Oncogenic Potential (CHOP): Separation from CHIP and Roads to AML. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030789"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1002\/ajh.25265","article-title":"Cytogenetic abnormalities in systemic mastocytosis: WHO subcategory-specific incidence and prognostic impact among 348 informative cases","volume":"93","author":"Shah","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"17","DOI":"10.5045\/br.2016.51.1.17","article-title":"A scientific treatment approach for acute mast cell leukemia: Using a strategy based on next-generation sequencing data","volume":"51","author":"Youk","year":"2016","journal-title":"Blood Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"730503","DOI":"10.3389\/fonc.2021.730503","article-title":"Comprehensive Clinicopathologic and Molecular Analysis of Mast Cell Leukemia With Associated Hematologic Neoplasm: A Report and In-Depth Study of 5 Cases","volume":"11","author":"Li","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.1038\/bcj.2014.94","article-title":"Novel recurrent mutations in ethanolamine kinase 1 (ETNK1) gene in systemic mastocytosis with eosinophilia and chronic myelomonocytic leukemia","volume":"5","author":"Lasho","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1182\/blood.2019004509","article-title":"Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis","volume":"137","author":"Toledo","year":"2021","journal-title":"Blood"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1182\/blood.2020010456","article-title":"\u201cMast\u201dering drug discovery with iPSCs","volume":"137","author":"Dorrance","year":"2021","journal-title":"Blood"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Shomali, W., and Gotlib, J. (2021). Response Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062983"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41576-019-0100-z","article-title":"Induced pluripotent stem cells in disease modelling and drug discovery","volume":"20","author":"Rowe","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"657","DOI":"10.7326\/0003-4819-146-9-200705010-00009","article-title":"Systematic review: Agranulocytosis induced by nonchemotherapy drugs","volume":"146","author":"Andersohn","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1056\/NEJM198706253162603","article-title":"Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis","volume":"316","author":"Schwartz","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.iac.2006.05.010","article-title":"Diagnostic value of tryptase in anaphylaxis and mastocytosis","volume":"26","author":"Schwartz","year":"2006","journal-title":"Immunol. Allergy Clin. N. 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