Chromosome 5q deletion drives evolution to aneuploidy in an iPSC model of complex karyotype leukemia

Aneuploidy is a hallmark of a unique group of high-risk myeloid malignancies including acute myeloid leukemias (AML), known as AML with complex karyotype (AML-CK). AML-CK is nearly universally associated with TP53 mutations and deletions on the long arm of chromosome 5 (del(5q)), however, the drivers and trajectories of AML-CK evolution have not been established. We performed single cell transcriptomics on iPSC based hematopoietic progenitor cell model of TP53 mutant/TP53 mutant + del5q driven to CK. Comparisons were performed between 2 AML-CK primary patient samples (R332, RO20518) and 2 isolated del5q MDS parient samples (AGC, TWN).