Chromosome 5q deletion drives evolution of aneuploidy in myeloid neoplasms with complex karyotype.

Chromosome 5q deletion combined with TP53 mutations drives stepwise aneuploidy evolution in myeloid neoplasms with complex karyotypes.

• Why it matters: Understanding the mechanisms behind chromosomal abnormalities in high-risk AML-CK is crucial for developing targeted therapies, as these abnormalities are linked to poor prognosis and treatment resistance.
• What they did: Using a patient-derived iPSC model, the study tracked chromosome changes at single-cell resolution, revealing that TP53-mutant HSPCs with del(5q) acquire complex chromosomal alterations stepwise, mirroring patient data.
• The result: A shared gene expression signature was identified in aneuploid HSPCs, highlighting BCL2-related vulnerabilities that can be targeted with venetoclax, offering potential therapeutic strategies for AML-CK.