{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:04:03Z","timestamp":1779815043338,"version":"3.53.1"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RUNX1 alterations contribute to pediatric myeloid malignancies through both germline predisposition syndromes and somatic leukemogenic events, but their clinical and biological significance in children remains incompletely defined. This retrospective single-center study evaluated six pediatric patients with myelodysplastic syndromes or acute leukemias harboring RUNX1 variants, integrating clinical, cytogenetic, and targeted next-generation sequencing data, with germline status confirmed using non-hematopoietic tissues. Three patients carried germline RUNX1 variants, characterized by antecedent cytopenias, dysplastic features, and increased treatment-related toxicity, including severe infections, persistent cytopenias, and transplant-related mortality. In contrast, somatic RUNX1 alterations were associated with overt high-risk disease, frequently accompanied by complex cytogenetics or monosomy 7, and demonstrated heterogeneous outcomes ranging from sustained remission to post-transplant relapse. Mixed-phenotype acute leukemia was observed in both groups. These findings support a model of RUNX1-driven leukemogenesis, in which germline and somatic alterations represent distinct yet interconnected trajectories, while highlighting the importance of distinguishing variant origin for risk stratification, donor selection, and therapeutic decision-making in pediatric myeloid malignancies. Given the small cohort size, the findings remain descriptive and require validation in larger prospective studies.<\/jats:p>","DOI":"10.3390\/ijms27114805","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:17:58Z","timestamp":1779812278000},"page":"4805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RUNX1 Alterations in Pediatric Myeloid Malignancies: Divergent Germline and Somatic Trajectories"],"prefix":"10.3390","volume":"27","author":[{"given":"Ana Maria","family":"Bic\u01ce","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Pediatrics, and Bone Marrow Transplantation Unit, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3706-6620","authenticated-orcid":false,"given":"Andra Daniela","family":"Marcu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Pediatrics, and Bone Marrow Transplantation Unit, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9039-5859","authenticated-orcid":false,"given":"Cristina Georgiana","family":"Jercan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Pediatrics, and Bone Marrow Transplantation Unit, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-5479","authenticated-orcid":false,"given":"Leti\u021bia Elena","family":"Radu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Pediatrics, and Bone Marrow Transplantation Unit, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3253-7341","authenticated-orcid":false,"given":"Irina","family":"Avramescu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Pediatrics, and Bone Marrow Transplantation Unit, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cerasela","family":"Jardan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Hematology Laboratory, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dumitru","family":"Jardan","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, MedLife, 010719 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onda Tabita","family":"C\u01celug\u01ceru","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Hematology Laboratory, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mambet","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Hematology, Emergency University Hospital Bucharest, 050098 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6031-8190","authenticated-orcid":false,"given":"Anca","family":"Coli\u021b\u01ce","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania"},{"name":"Department of Pediatrics, and Bone Marrow Transplantation Unit, Fundeni Clinical Institute, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1182\/blood-2017-09-765214","article-title":"How I treat myelodysplastic syndromes of childhood","volume":"131","author":"Locatelli","year":"2018","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/sj.leu.2402765","article-title":"A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases","volume":"17","author":"Hasle","year":"2003","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/j.1365-2141.2007.06958.x","article-title":"Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia: Molecular classification and treatment options","volume":"140","author":"Niemeyer","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.blre.2010.03.002","article-title":"Pathophysiology and management of inherited bone marrow failure syndromes","volume":"24","author":"Shimamura","year":"2010","journal-title":"Blood Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.3324\/haematol.2010.025619","article-title":"Inherited bone marrow failure syndromes","volume":"95","author":"Dokal","year":"2010","journal-title":"Haematologica"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.3324\/haematol.2023.282949","article-title":"Shwachman-Diamond syndromes: Clinical, genetic, and biochemical insights from the rare variants","volume":"108","author":"Kawashima","year":"2023","journal-title":"Haematologica"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bannon, S.A., and DiNardo, C.D. (2016). Hereditary Predispositions to Myelodysplastic Syndrome. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060838"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1182\/blood-2013-07-515528","article-title":"GATA2 deficiency: A protean disorder of hematopoiesis, lymphatics, and immunity","volume":"123","author":"Spinner","year":"2014","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Marcu, A.D., Bica, A.M., Jercan, C.G., Radu, L.E., Serbanica, A.N., Jardan, D., Colita, A., Dima, S.O., Tomuleasa, C., and Tanase, A.D. (2025). Insights into Pediatric GATA2-Related MDS: Unveiling Challenges in Clinical Practice. Biomedicines, 13.","DOI":"10.3390\/biomedicines13040827"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1182\/blood-2015-09-669937","article-title":"Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents","volume":"127","author":"Wlodarski","year":"2016","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/ng.3569","article-title":"SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7","volume":"48","author":"Narumi","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1182\/blood-2016-10-743302","article-title":"Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms","volume":"129","author":"Tesi","year":"2017","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1053\/j.seminhematol.2017.04.006","article-title":"RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM)","volume":"54","author":"Schlegelberger","year":"2017","journal-title":"Semin. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/ajmg.a.38142","article-title":"Childhood cancer predisposition syndromes\u2014A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology","volume":"173","author":"Ripperger","year":"2017","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Brettingham-Moore, K.H., Taberlay, P.C., and Holloway, A.F. (2015). Interplay between Transcription Factors and the Epigenome: Insight from the Role of RUNX1 in Leukemia. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00499"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19512","DOI":"10.1074\/jbc.M309074200","article-title":"Isoforms of the Ets transcription factor NERF\/ELF-2 physically interact with AML1 and mediate opposing effects on AML1-mediated transcription of the B cell-specific blk gene","volume":"279","author":"Cho","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1038\/sj.emboj.7601675","article-title":"Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C\/EBPalpha interaction","volume":"26","author":"Fujimoto","year":"2007","journal-title":"EMBO J."},{"key":"ref_19","first-page":"99","article-title":"Role of RUNX Family Transcription Factors in DNA Damage Response","volume":"43","author":"Samarakkody","year":"2020","journal-title":"Mol. Cells"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1615\/CritRevOncog.v16.i1-2.80","article-title":"RUNX1 mutations in clonal myeloid disorders: From conventional cytogenetics to next generation sequencing, a story 40 years in the making","volume":"16","author":"Mangan","year":"2011","journal-title":"Crit. Rev. Oncog."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.12659\/MSM.910916","article-title":"Identification of Key Genes and Pathways Associated with RUNX1 Mutations in Acute Myeloid Leukemia Using Bioinformatics Analysis","volume":"24","author":"Zhu","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1182\/bloodadvances.2019000901","article-title":"RUNX1-mutated families show phenotype heterogeneity and a somatic mutation profile unique to germline predisposed AML","volume":"4","author":"Brown","year":"2020","journal-title":"Blood Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1182\/blood-2017-11-814442","article-title":"RUNX1 mutations in pediatric acute myeloid leukemia are associated with distinct genetic features and an inferior prognosis","volume":"131","author":"Yamato","year":"2018","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1080\/16078454.2020.1858598","article-title":"Prognostic effect of RUNX1 mutations in myelodysplastic syndromes: A meta-analysis","volume":"25","author":"He","year":"2020","journal-title":"Hematology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1182\/blood.2022017764","article-title":"The spectrum of GATA2 deficiency syndrome","volume":"141","author":"Calvo","year":"2023","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Khan, M., Cortes, J., Kadia, T., Naqvi, K., Brandt, M., Pierce, S., Patel, K.P., Borthakur, G., Ravandi, F., and Konopleva, M. (2017). Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081618"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kasahara, K., Shiina, M., Fukuda, I., Ogata, K., and Nakamura, H. (2017). Molecular mechanisms of cooperative binding of transcription factors Runx1-CBFbeta-Ets1 on the TCRalpha gene enhancer. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172654"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"33088","DOI":"10.1074\/jbc.M303973200","article-title":"Energetic contribution of residues in the Runx1 Runt domain to DNA binding","volume":"278","author":"Li","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.1182\/blood-2009-05-223784","article-title":"AML1\/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: Prognostic implication and interaction with other gene alterations","volume":"114","author":"Tang","year":"2009","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/S0969-2126(02)00853-5","article-title":"DNA recognition by the RUNX1 transcription factor is mediated by an allosteric transition in the RUNT domain and by DNA bending","volume":"10","author":"Bartfeld","year":"2002","journal-title":"Structure"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1182\/bloodadvances.2019000644","article-title":"ClinGen Myeloid Malignancy Variant Curation Expert Panel recommendations for germline RUNX1 variants","volume":"3","author":"Luo","year":"2019","journal-title":"Blood Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/ng.3586","article-title":"Protein-structure-guided discovery of functional mutations across 19 cancer types","volume":"48","author":"Niu","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.3324\/haematol.11256","article-title":"Inherited thrombocytopenias","volume":"92","author":"Nurden","year":"2007","journal-title":"Haematologica"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1182\/blood.2023019746","article-title":"Natural history study of patients with familial platelet disorder with associated myeloid malignancy","volume":"142","author":"Cunningham","year":"2023","journal-title":"Blood"},{"key":"ref_35","unstructured":"Natalie Deuitch, M., Elizabeth Broadbridge, C.G.C., Lea Cunningham, B.S., and Paul Liu, M.D. (2021). PhD RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies. GeneReviews\u00ae [Internet], University of Washington, Seattle. Mar 4 [Updated 2025 Dec 4]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1182\/bloodadvances.2023011165","article-title":"Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy","volume":"8","author":"Yu","year":"2024","journal-title":"Blood Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e70057","DOI":"10.1002\/hem3.70057","article-title":"Disease characteristics and outcomes of acute myeloid leukemia in germline RUNX1 deficiency (Familial Platelet Disorder with associated Myeloid Malignancy)","volume":"9","author":"Ernst","year":"2025","journal-title":"HemaSphere"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1182\/blood-2023-187600","article-title":"Bone Marrow, Laboratory, and Clinical Features in Pediatric Patients with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancy (FPDMM)","volume":"142","author":"Patel","year":"2023","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Arai, H., Matsui, H., Chi, S., Utsu, Y., Masuda, S., Aotsuka, N., and Minami, Y. (2024). Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010652"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Forster, A., Decker, M., Schlegelberger, B., and Ripperger, T. (2022). Beyond Pathogenic RUNX1 Germline Variants: The Spectrum of Somatic Alterations in RUNX1-Familial Platelet Disorder with Predisposition to Hematologic Malignancies. Cancers, 14.","DOI":"10.3390\/cancers14143431"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6092","DOI":"10.1182\/bloodadvances.2023010045","article-title":"Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in RUNX1, GATA2, and DDX41","volume":"7","author":"Homan","year":"2023","journal-title":"Blood Adv."},{"key":"ref_42","first-page":"1974","article-title":"Germline and somatic genetic landscape of pediatric myelodysplastic syndromes","volume":"110","author":"Kotmayer","year":"2025","journal-title":"Haematologica"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8457","DOI":"10.1002\/cam4.3467","article-title":"Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique","volume":"9","author":"Wang","year":"2020","journal-title":"Cancer Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1038\/s41375-023-01919-8","article-title":"RUNX1 mutation has no prognostic significance in paediatric AML: A retrospective study of the AML-BFM study group","volume":"37","author":"Sendker","year":"2023","journal-title":"Leukemia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41586-018-0436-0","article-title":"The genetic basis and cell of origin of mixed phenotype acute leukaemia","volume":"562","author":"Alexander","year":"2018","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Van der Kouwe, E., and Staber, P.B. (2019). RUNX1-ETO: Attacking the Epigenome for Genomic Instable Leukemia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020350"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/leu.2012.49","article-title":"Depletion of RUNX1\/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding","volume":"26","author":"Ptasinska","year":"2012","journal-title":"Leukemia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/j.celrep.2017.05.005","article-title":"RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML","volume":"19","author":"Loke","year":"2017","journal-title":"Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Romanova, E.I., Zubritskiy, A.V., Lioznova, A.V., Ogunleye, A.J., Golotin, V.A., Guts, A.A., Lennartsson, A., Demidov, O.N., and Medvedeva, Y.A. (2022). RUNX1\/CEBPA Mutation in Acute Myeloid Leukemia Promotes Hypermethylation and Indicates for Demethylation Therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911413"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s11684-020-0815-4","article-title":"Distinct gene expression pattern of RUNX1 mutations coordinated by target repression and promoter hypermethylation in acute myeloid leukemia","volume":"16","author":"Li","year":"2022","journal-title":"Front. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1182\/blood.2019004292","article-title":"Hematopoietic stem cells acquire survival advantage by loss of RUNX1 methylation identified in familial leukemia","volume":"136","author":"Matsumura","year":"2020","journal-title":"Blood"},{"key":"ref_52","first-page":"1398","article-title":"Epigenetics and mutations in chronic myeloproliferative neoplasms","volume":"96","author":"Vannucchi","year":"2011","journal-title":"Haematologica"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12943-018-0881-2","article-title":"RUNX1 upregulation via disruption of long-range transcriptional control by a novel t(5;21)(q13;q22) translocation in acute myeloid leukemia","volume":"17","author":"Cheng","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/s41587-019-0332-7","article-title":"Single-cell multiomic analysis identifies regulatory programs in mixed-phenotype acute leukemia","volume":"37","author":"Granja","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/ajh.70116","article-title":"Acute Leukemias of Ambiguous Lineage with RUNX1 Mutations Show Similar Prognosis Compared to Acute Myeloid Leukemia with RUNX1 Mutations: A Study from the Bone Marrow Pathology Group","volume":"101","author":"Kirtek","year":"2026","journal-title":"Am. J. Hematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"107665","DOI":"10.1016\/j.leukres.2025.107665","article-title":"Molecular genetic characterization of mixed-phenotype acute leukemia (MPAL) with BCR::ABL1 fusion","volume":"151","author":"Shi","year":"2025","journal-title":"Leuk. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1038\/s41467-018-04924-z","article-title":"Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes","volume":"9","author":"Takahashi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s10689-025-00443-1","article-title":"Myelodysplastic syndrome with dual germline RUNX1 and DDX41 variants: A rare genetic predisposition case","volume":"24","author":"Bove","year":"2025","journal-title":"Fam. Cancer"},{"key":"ref_59","unstructured":"Adam, M.P., Bick, S., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies, GeneReviews((R))."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e321","DOI":"10.1097\/HS9.0000000000000321","article-title":"Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up","volume":"3","author":"Baliakas","year":"2019","journal-title":"HemaSphere"},{"key":"ref_61","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Sureda, A.C., Greco R\u2019 Kr\u00f6ger, S., and Carreras, N. (2024). The EBMT Handbook, Springer. [2nd ed.].","DOI":"10.1007\/978-3-031-44080-9"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:20:07Z","timestamp":1779812407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":62,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114805"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114805","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]}}}