{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:40:05Z","timestamp":1792813205243,"version":"4.5.0"},"reference-count":59,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Interdisciplinary Center for Clinical Research","award":["B-411"],"award-info":[{"award-number":["B-411"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: Large-cell transformation (LCT) of mycosis fungoides (MF) has been associated with a higher risk of relapse and progression and, consequently, restricted prognosis. Its molecular pathogenesis has not been elucidated yet. Materials and Methods: In order to address molecular mechanisms of LCT, we performed hybrid capture panel-based sequencing of skin biopsies from 10 patients suffering from MF with LCT versus 17 patients without LCT including follow-up biopsies during clinical course, respectively (51 samples in total). The analyzed patients were attributed to three different groups based on the presence of LCT and clinical behavior. Results: While indolent MF cases without LCT did not show pathogenic driver mutations, a high rate of oncogenic alterations was detected in patients with LCT and aggressive clinical courses. Various genes of different oncogenic signaling pathways, including the MAPK and JAK-STAT signaling pathways, as well as epigenetic modifiers were affected. A high inter-individual and distinctive intra-individual mutation diversity was observed. Oncogenic RAS mutations were exclusively detected in patients with LCT. Conclusion: Our data demonstrate that LCT transition of MF is associated with increased frequency of somatic mutations in cancer-associated genes. In particular, the activation of RAS signaling\u2014together with epigenetic dysregulation\u2014may crucially contribute to the molecular pathogenesis of the LCT phenotype, thus conveying its adverse clinical behavior.<\/jats:p>","DOI":"10.3390\/cancers13215512","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T12:39:42Z","timestamp":1635856782000},"page":"5512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Targeted Deep Sequencing of Mycosis Fungoides Reveals Intracellular Signaling Pathways Associated with Aggressiveness and Large Cell Transformation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-2554","authenticated-orcid":false,"given":"Marion","family":"Wobser","sequence":"first","affiliation":[{"name":"Venereology and Allergology and Skin Cancer Center, Department of Dermatology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-4751","authenticated-orcid":false,"given":"Sabine","family":"Roth","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Mainfranken, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Institute of Pathology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5472-8692","authenticated-orcid":false,"given":"Silke","family":"Appenzeller","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-2324","authenticated-orcid":false,"given":"Roland","family":"Houben","sequence":"additional","affiliation":[{"name":"Venereology and Allergology and Skin Cancer Center, Department of Dermatology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-8194","authenticated-orcid":false,"given":"David","family":"Schrama","sequence":"additional","affiliation":[{"name":"Venereology and Allergology and Skin Cancer Center, Department of Dermatology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-9848","authenticated-orcid":false,"given":"Matthias","family":"Goebeler","sequence":"additional","affiliation":[{"name":"Venereology and Allergology and Skin Cancer Center, Department of Dermatology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-0747","authenticated-orcid":false,"given":"Eva","family":"Geissinger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Pathology Practice, 85049 Ingolstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7282-8374","authenticated-orcid":false,"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Mainfranken, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Institute of Pathology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3093-3114","authenticated-orcid":false,"given":"Katja","family":"Maurus","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Mainfranken, University Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Institute of Pathology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1200\/JCO.2015.61.7142","article-title":"Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and S\u00e9zary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model","volume":"33","author":"Scarisbrick","year":"2015","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1111\/bjd.15214","article-title":"Prognostic factors in mycosis fungoides: International advances in the validation of prognostic indices","volume":"176","author":"Scarisbrick","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_3","first-page":"265","article-title":"Transformation of cutaneous T cell lymphoma to large cell lymphoma. A clinicopathologic and immunologic study","volume":"132","author":"Salhany","year":"1988","journal-title":"Am. J. Pathol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1200\/JCO.1995.13.7.1751","article-title":"Large-cell transformation following detection of minimal residual disease in cutaneous T-cell lymphoma: Molecular and in situ analysis of a single neoplastic T-cell clone expressing the identical T-cell receptor","volume":"13","author":"Wolfe","year":"1995","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/1523-1747.ep12365416","article-title":"Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma","volume":"101","author":"Wood","year":"1993","journal-title":"J. Investig. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.jaad.2011.12.011","article-title":"Recognizing large-cell transformation of mycosis fungoides","volume":"67","author":"Herrmann","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00000372-199802000-00001","article-title":"Histologic and immunophenotypic features prior to transformation in patients with transformed cutaneous T-cell lymphoma: Is CD25 expression in skin biopsy samples predictive of large cell transformation in cutaneous T-cell lymphoma?","volume":"20","author":"Stefanato","year":"1998","journal-title":"Am. J. Derm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/00000478-199206000-00002","article-title":"Clinicopathologic and immunologic features associated with transformation of mycosis fungoides to large-cell lymphoma","volume":"16","author":"Cerroni","year":"1992","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1365-2133.2007.08008.x","article-title":"Transformed mycosis fungoides: Clinicopathological features and outcome","volume":"157","author":"Barberio","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1182\/blood.V92.4.1150","article-title":"Transformation of Mycosis Fungoides\/Sezary Syndrome: Clinical Characteristics and Prognosis","volume":"92","author":"Diamandidou","year":"1998","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1046\/j.1523-1747.1998.00167.x","article-title":"Overexpression of p53 protein in cutaneous T cell lymphoma: Relationship to large cell transformation and disease progression","volume":"110","author":"Li","year":"1998","journal-title":"J. Investig. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1182\/blood-2008-05-154609","article-title":"Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation","volume":"112","author":"Arulogun","year":"2008","journal-title":"Blood"},{"key":"ref_13","first-page":"2212","article-title":"Transformation of mycosis fungoides: Clinicopathological and prognostic features of 45 cases. French Study Group of Cutaneious Lymphomas","volume":"95","author":"Vergier","year":"2000","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1182\/blood-2011-08-376319","article-title":"Prognostic factors in transformed mycosis fungoides: A retrospective analysis of 100 cases","volume":"119","author":"Benner","year":"2012","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/hon.2900080406","article-title":"Clinical features associated with transformation of cerebriform T-cell lymphoma to a large cell process","volume":"8","author":"Greer","year":"1990","journal-title":"Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4730","DOI":"10.1200\/JCO.2009.27.7665","article-title":"Survival outcomes and prognostic factors in mycosis fungoides\/S\u00e9zary syndrome: Validation of the revised International Society for Cutaneous Lymphomas\/European Organisation for Research and Treatment of Cancer staging proposal","volume":"28","author":"Agar","year":"2010","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1182\/blood-2007-03-055749","article-title":"Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","volume":"110","author":"Olsen","year":"2007","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1182\/blood-2018-11-881268","article-title":"The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas","volume":"133","author":"Willemze","year":"2019","journal-title":"Blood"},{"key":"ref_19","first-page":"112","article-title":"S2k Guidelines\u2014Cutaneous Lymphomas Update 2016\u2014Part 2: Treatment and Follow-up (ICD10 C82\u2013C86)","volume":"16","author":"Dippel","year":"2018","journal-title":"J. Der. Dtsch. Dermatol. Ges. J. Ger. Soc. Dermatol. JDDG"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/j.jid.2020.02.019","article-title":"Recurrent Oncogenic JAK and STAT Alterations in Cutaneous CD30-Positive Lymphoproliferative Disorders","volume":"140","author":"Maurus","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100034","DOI":"10.1016\/j.xjidi.2021.100034","article-title":"Oncogenic Mutations and Gene Fusions in CD30-Positive Lymphoproliferations and Clonally Related Mycosis Fungoides Occurring in the Same Patients","volume":"1","author":"Wobser","year":"2021","journal-title":"JID Innov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration","volume":"14","author":"Robinson","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1038\/s41598-021-83352-4","article-title":"Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma","volume":"11","author":"Jones","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1182\/blood-2013-05-504308","article-title":"PLCG1 mutations in cutaneous T-cell lymphomas","volume":"123","author":"Varela","year":"2014","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/2212697X03666160610085943","article-title":"Transforming Mutations of Jak3 (A573V and M511I) Show Differential Sensitivity to Selective Jak3 Inhibitors","volume":"3","author":"Martinez","year":"2016","journal-title":"Clin. Cancer Drugs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1073\/pnas.1700682114","article-title":"Cytokine receptor signaling is required for the survival of ALK- anaplastic large cell lymphoma, even in the presence of JAK1\/STAT3 mutations","volume":"114","author":"Chen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1158\/0008-5472.CAN-19-3682","article-title":"The Frequency of Ras Mutations in Cancer","volume":"80","author":"Prior","year":"2020","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1182\/blood.2020005734","article-title":"Active Akt signaling triggers CLL toward Richter transformation via overactivation of Notch1","volume":"137","author":"Kohlhaas","year":"2021","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/bjd.13476","article-title":"Diagnostic and prognostic significance of CDKN2A\/CDKN2B deletions in patients with transformed mycosis fungoides and primary cutaneous CD30-positive lymphoproliferative disease","volume":"172","author":"Benner","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/jid.2009.314","article-title":"IRF4 gene rearrangements define a subgroup of CD30-positive cutaneous T-cell lymphoma: A study of 54 cases","volume":"130","author":"Laharanne","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s12253-015-9897-8","article-title":"Altered microRNA expression in folliculotropic and transformed mycosis fungoides","volume":"21","author":"Csala","year":"2015","journal-title":"Pathol. Oncol. Res. POR"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1016\/j.jid.2018.05.007","article-title":"Loss of 5-Hydroxymethylcytosine Is an Epigenetic Biomarker in Cutaneous T-Cell Lymphoma","volume":"138","author":"Qiu","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1097\/PAS.0000000000000091","article-title":"CD20 antigen may be expressed by reactive or lymphomatous cells of transformed mycosis fungoides: Diagnostic and prognostic impact","volume":"37","author":"Carlotti","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/1346-8138.12305","article-title":"Immunological milieu in mycosis fungoides and S\u00e9zary syndrome","volume":"41","author":"Miyagaki","year":"2014","journal-title":"J. Derm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/ng.3370","article-title":"Genomic analysis of mycosis fungoides and S\u00e9zary syndrome identifies recurrent alterations in TNFR2","volume":"47","author":"Ungewickell","year":"2015","journal-title":"Nat Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1038\/ng.3444","article-title":"Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes","volume":"47","author":"Wang","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1182\/blood-2014-11-611194","article-title":"Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides","volume":"126","author":"McGirt","year":"2015","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1182\/blood-2010-09-305128","article-title":"High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS\/RAF\/MEK signaling cascade","volume":"117","author":"Kiessling","year":"2011","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Damsky, W.E., and Choi, J. (2016). Genetics of Cutaneous T Cell Lymphoma: From Bench to Bedside. Curr. Treat. Options Oncol., 17.","DOI":"10.1007\/s11864-016-0410-8"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1182\/blood-2009-11-251926","article-title":"Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: A biologic rationale for their distinct clinical behaviors","volume":"116","author":"Campbell","year":"2010","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1002\/cncr.28864","article-title":"The MAPK pathway across different malignancies: A new perspective","volume":"120","author":"Burotto","year":"2014","journal-title":"Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1182\/blood-2014-04-531871","article-title":"Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition","volume":"124","author":"Irving","year":"2014","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/ng.3356","article-title":"Genomic landscape of cutaneous T cell lymphoma","volume":"47","author":"Choi","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1056\/NEJMoa2103695","article-title":"Sotorasib for Lung Cancers with KRAS p.G12C Mutation","volume":"384","author":"Skoulidis","year":"2021","journal-title":"New Engl. J. Med."},{"key":"ref_46","first-page":"10","article-title":"Regulatory mechanisms governing chromatin organization and function","volume":"70","author":"Baubec","year":"2020","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s11899-019-00541-9","article-title":"Chromatin-Remodeled State in Lymphoma","volume":"14","author":"Liu","year":"2019","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrg.2016.13","article-title":"Epigenetic modulators, modifiers and mediators in cancer aetiology and progression","volume":"17","author":"Feinberg","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/j.celrep.2014.10.063","article-title":"Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation","volume":"9","author":"Wu","year":"2014","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nature06251","article-title":"An elaborate pathway required for Ras-mediated epigenetic silencing","volume":"449","author":"Gazin","year":"2007","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13045-019-0719-4","article-title":"Elucidating the mechanism of action of domatinostat (4SC-202) in cutaneous T cell lymphoma cells","volume":"12","author":"Wobser","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11899-010-0067-5","article-title":"The emerging role of histone deacetylase inhibitors in treating T-cell lymphomas","volume":"6","author":"Horwitz","year":"2011","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1038\/ng.3442","article-title":"The mutational landscape of cutaneous T cell lymphoma and S\u00e9zary syndrome","volume":"47","author":"Abate","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/j.jid.2016.03.042","article-title":"Epigenomic Analysis of S\u00e9zary Syndrome Defines Patterns of Aberrant DNA Methylation and Identifies Diagnostic Markers","volume":"136","author":"Slieker","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_55","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":"New Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1089\/jir.1998.18.915","article-title":"Analysis of the human and mouse promoter region of the non-Hodgkin\u2019s lymphoma-associated CD30 gene","volume":"18","author":"Croager","year":"1998","journal-title":"J. Int. Soc. Interferon Cytokine Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJMoa1110556","article-title":"JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis","volume":"366","author":"Harrison","year":"2012","journal-title":"New Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1182\/bloodadvances.2019001043","article-title":"A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease","volume":"4","author":"Schroeder","year":"2020","journal-title":"Blood Adv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e450","DOI":"10.3324\/haematol.2015.132837","article-title":"Mutated JAK kinases and deregulated STAT activity are potential therapeutic targets in cutaneous T-cell lymphoma","volume":"100","author":"Onaindia","year":"2015","journal-title":"Haematologica"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/21\/5512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:24:51Z","timestamp":1760167491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/21\/5512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,2]]},"references-count":59,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cancers13215512"],"URL":"https:\/\/doi.org\/10.3390\/cancers13215512","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,2]]}}}