RAS mutations in therapy-related acute myeloid leukemia after successful treatment of acute promyelocytic leukemia

摘要

In patients successfully treated for acute promyelocytic leukemia (APL) the occurrence of therapy related myeloid neoplasm (TMN) is rare, with an incidence reported from 1 to 6.5% in different studies [1,2]. Based on latency, associated cytogenetic findings and the presence or absence of antecedent myelodysplastic syndrome (MDS), the reported cases are a mixture of topoisomerase inhibitor-type and alky-lating agent-type [2]. At the molecular level, the mechanisms underlying the development of TMN are largely undefined. We report three cases of TMN in patients previously cured of APL. In these three patients, we used a mass spectrometry-based multiplex mutation detection approach to evaluate for 370 point mutations across 31 genes. The rationale for selecting this combination of genes was that they all were previously described in association with leukemia.