TY - JOUR
T1 - Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms
AU - Palomo, Laura
AU - Meggendorfer, Manja
AU - Hutter, Stephan
AU - Twardziok, Sven
AU - Ademà, Vera
AU - Fuhrmann, Irene
AU - Fuster-Tormo, Francisco
AU - Xicoy, Blanca
AU - Zamora, Lurdes
AU - Acha, Pamela
AU - Kerr, Cassandra M.
AU - Kern, Wolfgang
AU - Maciejewski, Jaroslaw P.
AU - Solé, Francesc
AU - Haferlach, Claudia
AU - Haferlach, Torsten
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/10
Y1 - 2020/10
N2 - 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 5 119), atypical chronic myeloid leukemia (aCML; n 5 71), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n 5 71), and MDS/MPN unclassifiable (MDS/MPN-U; n 5 106). 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.
AB - 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 5 119), atypical chronic myeloid leukemia (aCML; n 5 71), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n 5 71), and MDS/MPN unclassifiable (MDS/MPN-U; n 5 106). 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.
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U2 - 10.1182/BLOOD.2019004229
DO - 10.1182/BLOOD.2019004229
M3 - Article
C2 - 32573691
AN - SCOPUS:85093539016
SN - 0006-4971
VL - 136
SP - 1851
EP - 1862
JO - Blood
JF - Blood
IS - 16
ER -