Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia

Abstract

Key Points• Different driver mutations have distinct effects on phenotype of myelodysplastic syndromes (MDS) and myelodysplastic/ myeloproliferative neoplasms (MDS/MPN).• Accounting for driver mutations may allow a classification of these disorders that is considerably relevant for clinical decision-making. Irrespective of driver somatic mutations, a threshold of 5% bone marrow blasts retained a significant discriminant value for identifying cases with clonal evolution. Comutation of TET2 and SRSF2 was highly predictive of a myeloid neoplasm characterized by myelodysplasia and monocytosis, including but not limited to, chronic myelomonocytic leukemia. These results serve as a proof of concept that a molecular classification of myeloid neoplasms is feasible. (Blood. 2014;124(9):1513-1521

CMML: Clinical and molecular aspects

“…Mutations in TET2, SRSF2 and ASXL1 are by far the most frequent, being present in ~30-50% of cases each, and even though none of these oncogenes is specific of CMML amongst other myeloid neoplasms, the combination of TET2/SRSF2 mutations is highly suggestive of CMML [39]. As discussed below, mutations in signaling transduction genes are more frequent in patients with MP-CMML.…”

An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults

“…The prognostic relevance of gene mutations may differ among MDS/MPN. For instance, SF3B1 mutations have been found to be important prognostically in the RARS-T subgroup, 29,47 whereas their impact on the outcome of CMML patients remains to be investigated. How these aberrations may later be incorporated into risk models for these diseases remains unclear, and clarifying this information to properly incorporate these aberrations in prognostication is a priority.…”

Refractory anemia with ring sideroblasts and marked thrombocytosis cases harbor mutations in SF3B1 or other spliceosome genes accompanied by JAK2V617F and ASXL1 mutations

“…High frequencies have been detected only in small cohorts: 12.5% (n=24) 7 and 25.0% (n=12), 10 whereas a large multicenter study reported a frequency of only 1.1% (n=95).…”