| Autor: |
François Vergez, Laetitia Largeaud, Sarah Bertoli, Marie-Laure Nicolau, Jean-Baptiste Rieu, Inès Vergnolle, Estelle Saland, Audrey Sarry, Suzanne Tavitian, Françoise Huguet, Muriel Picard, Jean-Philippe Vial, Nicolas Lechevalier, Audrey Bidet, Pierre-Yves Dumas, Arnaud Pigneux, Isabelle Luquet, Véronique Mansat-De Mas, Eric Delabesse, Martin Carroll, Gwenn Danet-Desnoyers, Jean-Emmanuel Sarry, Christian Récher |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Blood Cancer Journal, Vol 12, Iss 8, Pp 1-11 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2044-5385 |
| DOI: |
10.1038/s41408-022-00712-7 |
| Popis: |
Abstract Classifications of acute myeloid leukemia (AML) patients rely on morphologic, cytogenetic, and molecular features. Here we have established a novel flow cytometry-based immunophenotypic stratification showing that AML blasts are blocked at specific stages of differentiation where features of normal myelopoiesis are preserved. Six stages of leukemia differentiation-arrest categories based on CD34, CD117, CD13, CD33, MPO, and HLA-DR expression were identified in two independent cohorts of 2087 and 1209 AML patients. Hematopoietic stem cell/multipotent progenitor-like AMLs display low proliferation rate, inv(3) or RUNX1 mutations, and high leukemic stem cell frequency as well as poor outcome, whereas granulocyte–monocyte progenitor-like AMLs have CEBPA mutations, RUNX1-RUNX1T1 or CBFB-MYH11 translocations, lower leukemic stem cell frequency, higher chemosensitivity, and better outcome. NPM1 mutations correlate with most mature stages of leukemia arrest together with TET2 or IDH mutations in granulocyte progenitors-like AML or with DNMT3A mutations in monocyte progenitors-like AML. Overall, we demonstrate that AML is arrested at specific stages of myeloid differentiation (SLA classification) that significantly correlate with AML genetic lesions, clinical presentation, stem cell properties, chemosensitivity, response to therapy, and outcome. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink