Phenotypically-defined stages of leukemia arrest predict main driver mutations subgroups, and outcome in acute myeloid leukemia.
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
16 08 2022
16 08 2022
Historique:
received:
22
02
2022
accepted:
26
07
2022
revised:
22
07
2022
entrez:
16
8
2022
pubmed:
17
8
2022
medline:
19
8
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35973983
doi: 10.1038/s41408-022-00712-7
pii: 10.1038/s41408-022-00712-7
pmc: PMC9381519
doi:
Substances chimiques
Core Binding Factor Alpha 2 Subunit
0
HLA-DR Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
117Informations de copyright
© 2022. The Author(s).
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