학술논문
Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms.
Document Type
Academic Journal
Author
Palomo L; Myelodysplastic Syndromes (MDS) Group, Josep Carreras Leukaemia Research Institute, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.; Meggendorfer M; Munich Leukemia Laboratory (MLL), Munich, Germany.; Hutter S; Munich Leukemia Laboratory (MLL), Munich, Germany.; Twardziok S; Munich Leukemia Laboratory (MLL), Munich, Germany.; Ademà V; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; and.; Fuhrmann I; Munich Leukemia Laboratory (MLL), Munich, Germany.; Fuster-Tormo F; Myelodysplastic Syndromes (MDS) Group, Josep Carreras Leukaemia Research Institute, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.; Xicoy B; Hematology Service, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Zamora L; Hematology Service, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Barcelona, Spain.; Acha P; Myelodysplastic Syndromes (MDS) Group, Josep Carreras Leukaemia Research Institute, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.; Kerr CM; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; and.; Kern W; Munich Leukemia Laboratory (MLL), Munich, Germany.; Maciejewski JP; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; and.; Solé F; Myelodysplastic Syndromes (MDS) Group, Josep Carreras Leukaemia Research Institute, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.; Haferlach C; Munich Leukemia Laboratory (MLL), Munich, Germany.; Haferlach T; Munich Leukemia Laboratory (MLL), Munich, Germany.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE
Subject
Language
English
Abstract
More than 90% of patients with myelodysplastic/myeloproliferative neoplasms (MDSs/MPNs) harbor somatic mutations in myeloid-related genes, but still, current diagnostic criteria do not include molecular data. We performed genome-wide sequencing techniques to characterize the mutational landscape of a large and clinically well-characterized cohort including 367 adults with MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 119), atypical chronic myeloid leukemia (aCML; n = 71), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 71), and MDS/MPN unclassifiable (MDS/MPN-U; n = 106). A total of 30 genes were recurrently mutated in ≥3% of the cohort. Distribution of recurrently mutated genes and clonal architecture differed among MDS/MPN subtypes. Statistical analysis revealed significant correlations between recurrently mutated genes, as well as genotype-phenotype associations. We identified specific gene combinations that were associated with distinct MDS/MPN subtypes and that were mutually exclusive with most of the other MDSs/MPNs (eg, TET2-SRSF2 in CMML, ASXL1-SETBP1 in aCML, and SF3B1-JAK2 in MDS/MPN-RS-T). Patients with MDS/MPN-U were the most heterogeneous and displayed different molecular profiles that mimicked the ones observed in other MDS/MPN subtypes and that had an impact on the outcome of the patients. Specific gene mutations also had an impact on the outcome of the different MDS/MPN subtypes, which may be relevant for clinical decision-making. Overall, the results of this study help to elucidate the heterogeneity found in these neoplasms, which can be of use in the clinical setting of MDS/MPN.
(© 2020 by The American Society of Hematology.)
(© 2020 by The American Society of Hematology.)