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

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.

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Publication Details

Journal
Blood Advances
Published
2024-10-10
DOI
https://doi.org/10.1182/bloodadvances.2024013648
Citations
4
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
1.82

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article

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

Inés Zugasti, Francesca Guijarro, Sandra Castaño‐Díez, Mònica López‐Guerra et al.
4 citations
Blood Advances
Acute Myeloid Leukemia Research
1.82
article

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

Inés Zugasti, Francesca Guijarro, Sandra Castaño‐Díez, Mònica López‐Guerra, José Francisco Falantes-González, Daniel Esteban, Jordi Esteve, Beate Betz, Xavier Calvo, Carlos Jiménez‐Vicente, Tzu Hua Chen‐Liang, Neus Amer-Salas, Elvira Mora, Helena Pomares, Ana Triguero, Alejandro Avendaño, Marı́a Rozman, María Díez‐Campelo, Mariam Ibáñez, Blanca Xicoy, Felicitas Schulz, Ester Carcelero, Marina Díaz‐Beyá, Teresa Bernal, Gemma Azaceta, José Ramón Álamo Moreno, Leonor Arenillas, Lurdes Zamora, Laura Palomo, Albert Cortés‐Bullich, Víctor Torrecillas-Mayayo, Jordi Vila, Aina Cardús, Cristina Notario Mc Donnell, Lucía Mont‐de Torres, Ulrich Germing
article en
4 citations

Abstract

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.

Blood AdvancesVol. 9(1)
Hebron University (PS), Universitat Autònoma de Barcelona (ES), Hospital Universitari i Politècnic La Fe (ES), Hospital Son Llatzer (ES), Hospital Universitario Nuestra Señora de Candelaria (ES), Düsseldorf University Hospital (DE), Hospital General Universitario Morales Meseguer (ES), Complejo Hospitalario de Salamanca (ES), Institut Català d'Oncologia (ES), Hospital Clínic de Barcelona (ES), Madrid Health Service (ES), Vall d'Hebron Hospital Universitari (ES), Hospital General Universitario De Valencia (ES), Hospital Del Mar (ES), Hospital Clínico Universitario Lozano Blesa (ES), Duran i Reynals Hospital (ES), Fundación Josep Carreras Contra la Leucemia (ES), CIBBIM-Nanomedicine (ES), Hospital Universitario Virgen del Rocío (ES), Hospital Universitari de Girona Doctor Josep Trueta (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Instituto de Investigación Sanitaria del Principado de Asturias (ES), Heinrich Heine University Düsseldorf (DE), Universitat de Barcelona (ES)
European Commission, Instituto de Salud Carlos III
Good health and well-being
Openalex Percentile: Top 14%
Acute Myeloid Leukemia Research
1.82
DOIOpen Access PDFOpenAlex
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