Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms.
Por:
Palomo L, Meggendorfer M, Hutter S, Twardziok S, Ademà V, Fuhrmann I, Fuster-Tormo F, Xicoy B, Zamora L, Acha P, Kerr CM, Kern W, Maciejewski JP, Solé F, Haferlach C and Haferlach T
Publicada:
15 oct 2020
Resumen:
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.
Filiaciones:
:
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
:
Hematology Service, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Barcelona, Spain
:
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
Bronze, Green Published
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