Phenotypic subtypes of leukaemic transformation in chronic myelomonocytic leukaemia.

Autor: Montalban-Bravo G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kanagal-Shamanna R; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Li Z; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Hammond D; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Chien K; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Rodriguez-Sevilla JJ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Sasaki K; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Jabbour E; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., DiNardo C; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Takahashi K; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Short N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Issa GC; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Pemmaraju N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kadia T; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Ravandi F; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Daver N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Borthakur G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Loghavi S; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Pierce S; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Bueso-Ramos C; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Kantarjian H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Garcia-Manero G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2023 Nov; Vol. 203 (4), pp. 581-592. Date of Electronic Publication: 2023 Aug 22.
DOI: 10.1111/bjh.19060
Abstrakt: Chronic myelomonocytic leukaemia (CMML) is a haematological disorder with high risk of transformation to acute myeloid leukaemia (AML). To characterize the phenotypic and genomic patterns of CMML progression, we evaluated a cohort of 189 patients with AML evolving from CMML. We found that transformation occurs through distinct trajectories characterized by genomic profiles and clonal evolution: monocytic (Mo-AML, 53%), immature myeloid (My-AML, 43%) or erythroid (Ery-AML, 2%). Mo-AML, characterized by expansion of monoblasts and promonocytes (low CD34, CD117 expression; high CD14, CD33, CD56 and CD64 expression), were defined by SRSF2, TET2 and RAS pathway mutation co-dominance and were more likely to evolve from SRSF2-TET2 co-mutant CMML through emergence/expansion of RAS pathway mutant clones. Conversely, My-AML, characterized by expansion of immature myeloid blasts (high frequency of CD34, CD38, CD117; low frequency of CD14, CD64 and CD56 expression) were less likely to exhibit SRSF2-TET2 co-mutations or RAS pathway mutations and had higher frequency of CEBPA mutations. Ery-AML was defined by complex karyotypes and TP53 mutations. A trend towards improved OS and EFS with hypomethylating agent-venetoclax combination was observed in My-AML, but not Mo-AML. These findings define distinct progression of CMML and set the basis for future studies evaluating the role of phenotype-specific therapeutics.
(© 2023 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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