Deciphering Potential Molecular Signatures to Differentiate Acute Myeloid Leukemia (AML) with BCR::ABL1 from Chronic Myeloid Leukemia (CML) in Blast Crisis.

Autor: Boucher L; CHU de Poitiers, Service de Cancérologie Biologique, F86000 Poitiers, France., Sorel N; CHU de Poitiers, Service de Cancérologie Biologique, F86000 Poitiers, France., Desterke C; Faculté de Médecine, Université Paris Saclay, F94270 Le Kremlin-Bicêtre, France., Chollet M; CHU de Poitiers, Service d'Hématologie Biologique, F86000 Poitiers, France., Rozalska L; CHU de Poitiers, Service d'Hématologie Biologique, F86000 Poitiers, France., Gallego Hernanz MP; CHU de Poitiers, Service d'Oncologie Hématologique et Thérapie Cellulaire, F86000 Poitiers, France.; INSERM, CIC-P 1402, F86000 Poitiers, France., Cayssials E; CHU de Poitiers, Service d'Oncologie Hématologique et Thérapie Cellulaire, F86000 Poitiers, France.; INSERM, CIC-P 1402, F86000 Poitiers, France., Raimbault A; CHU de Poitiers, Service de Cancérologie Biologique, F86000 Poitiers, France.; CHU de Poitiers, Service d'Hématologie Biologique, F86000 Poitiers, France., Bennaceur-Griscelli A; Faculté de Médecine, Université Paris Saclay, F94270 Le Kremlin-Bicêtre, France.; INSERM U1310, F94807 Villejuif, France.; INGESTEM-ESTeam Paris Sud, F94800 Villejuif, France.; Service d'Onco-Hématologie, Hôpital Paul Brousse, AP-HP Université Paris Saclay, F94804 Villejuif, France.; Service d'Hématologie, Hôpital Bicêtre, AP-HP Université Paris Saclay, F94270 Le Kremlin-Bicêtre, France., Turhan AG; Faculté de Médecine, Université Paris Saclay, F94270 Le Kremlin-Bicêtre, France.; INSERM U1310, F94807 Villejuif, France.; INGESTEM-ESTeam Paris Sud, F94800 Villejuif, France.; Service d'Onco-Hématologie, Hôpital Paul Brousse, AP-HP Université Paris Saclay, F94804 Villejuif, France.; Service d'Hématologie, Hôpital Bicêtre, AP-HP Université Paris Saclay, F94270 Le Kremlin-Bicêtre, France., Chomel JC; CHU de Poitiers, Service de Cancérologie Biologique, F86000 Poitiers, France.; INSERM U1310, F94807 Villejuif, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Oct 22; Vol. 24 (20). Date of Electronic Publication: 2023 Oct 22.
DOI: 10.3390/ijms242015441
Abstrakt: Acute myeloid leukemia (AML) with BCR::ABL1 has recently been recognized as a distinct subtype in international classifications. Distinguishing it from myeloid blast crisis chronic myeloid leukemia (BC-CML) without evidence of a chronic phase (CP), remains challenging. We aimed to better characterize this entity by integrating clonal architecture analysis, mutational landscape assessment, and gene expression profiling. We analyzed a large retrospective cohort study including CML and AML patients. Two AML patients harboring a BCR::ABL1 fusion were included in the study. We identified BCR::ABL1 fusion as a primary event in one patient and a secondary one in the other. AML-specific variants were identified in both. Real-time RT-PCR experiments demonstrated that CD25 mRNA is overexpressed in advanced-phase CML compared to AML. Unsupervised principal component analysis showed that AML harboring a BCR::ABL1 fusion was clustered within AML. An AML vs. myeloid BC-CML differential expression signature was highlighted, and while ID4 (inhibitor of DNA binding 4) mRNA appears undetectable in most myeloid BC-CML samples, low levels are detected in AML samples. Therefore, CD25 and ID4 mRNA expression might differentiate AML with BCR::ABL1 from BC-CML and assign it to the AML group. A method for identifying this new WHO entity is then proposed. Finally, the hypothesis of AML with BCR::ABL1 arising from driver mutations on a BCR::ABL1 background behaving as a clonal hematopoiesis mutation is discussed. Validation of our data in larger cohorts and basic research are needed to better understand the molecular and cellular aspects of AML with a BCR::ABL1 entity.
Databáze: MEDLINE
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