Decoding Chromosome 5q Deletion: Driving Aneuploidy Evolution and Therapeutic Strategies in Complex Karyotype Myeloid Neoplasms

Highlight

1. Chromosome 5q deletion is a critical driver of aneuploidy development in hematopoietic stem and progenitor cells (HSPCs) bearing TP53 mutations in AML with complex karyotype (AML-CK).
2. Stepwise acquisition of numerical and structural chromosome abnormalities parallels an evolutionary trajectory leading to highly aneuploid malignant clones.
3. Aneuploid HSPCs share a distinct gene expression signature including upregulation of PTEN, cohesin components, and the antiapoptotic gene BCL2.
4. Targeting the BCL2-dependent aneuploid clones with venetoclax demonstrates therapeutic potential, although lineage switch mechanisms may confer resistance.

Study Background