AML typical mutations (CEBPA, FLT3, NPM1) identify a high-risk chronic myelomonocytic leukemia independent of CPSS molecular

Abstract

Leucèmia mielomonocítica crònica; Leucèmia mieloide aguda; Mutació

Leucemia mielomonocítica crónica; Leucemia mieloide aguda; Mutación

Chronic myelomonocytic leukemia; Acute myeloid leukemia; Mutation

Mutations commonly associated with acute myeloid leukemia (AML), such as CEBPA, FLT3, IDH1/2, and NPM1, are rarely found in chronic myelomonocytic leukemia (CMML), and their prognostic significance in CMML has not been clearly identified. In 127 patients with CMML, we have retrospectively analyzed next-generation sequencing and polymerase chain reaction data from bone marrow samples collected at the time of CMML diagnosis. Seven patients harbored CEBPA mutations, 8 FLT3 mutations, 12 IDH1 mutations, 26 IDH2 mutations, and 11 NPM1 mutations. Patients with CMML harboring CEBPA, FLT3, and/or NPM1 mutations (mutCFN) more frequently had the myeloproliferative subtype, a high prevalence of severe cytopenia, and elevated blast counts. Regardless of their CMML Prognostic Scoring System molecular classification, mutCFN patients with CMML had a poor prognosis, and the multivariate analysis identified mutCFN as an independent marker of overall survival. The genetic profile of these mutCFN patients with CMML closely resembled that of patients with AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible. Furthermore, certain targeted therapies approved for use in AML should be considered.

This study was supported by Contractes Clínic de Recerca Emili Letang-Josep Font 2021 grants from the Hospital Clínic de Barcelona; Instituto de Salud Carlos III through the project “FIS PI22/01660” cofunded by the European Union (M.D.-B. and J.E.); and Convocatoria d ` ’Intensificacio Interna per als professionals de ´ l’HCB 2023 (M.D.-B.) and Collaboration Scholarship, financed by the Spanish Ministry of Education (V.T.-M.).