Clonal evolution and apoptosis resistance in myelodysplastic neoplasms and acute myeloid leukemia under treatment: insights from integrative longitudinal profiling.

ABSTRACT: Treatment of high-risk Myelodysplastic Neoplasms (hr-MDS) and (secondary) Acute Myeloid Leukemia (AML) remains a clinical challenge. The combination of azacitidine and venetoclax (aza/ven) may improve treatment outcomes, but still fails in a significant fraction of patients. We established a single-center collection of longitudinal samples from patients with MDS and AML/sAML and performed comprehensive genetic, proteomic and functional apoptosis profiling to identify biomarkers and targetable escape mechanisms to aza/ven. Baseline genetic characterization (n = 55) identified high-risk genetic alterations, while longitudinal analyses (n = 268, mean 8.7 [3-20] timepoints) revealed distinct genetic profiles of clonal evolution. Functional BH3-profiling at treatment initiation identified heter

SUBMITTER: Mazzeo P 

PROVIDER: S-EPMC12634422 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature