Timing and trajectory of BCR::ABL1-driven chronic myeloid leukaemia.

ABSTRACT: Mutation of some genes drives uncontrolled cell proliferation and cancer. The Philadelphia chromosome in chronic myeloid leukaemia (CML) provided the very first such genetic link to cancer^1,2. However, little is known about the trajectory to CML, the rate of BCR::ABL1 clonal expansion and how this affects disease. Using whole-genome sequencing of 1,013 haematopoietic colonies from nine patients with CML aged 22 to 81 years, we reconstruct phylogenetic trees of haematopoiesis. Intronic breaks in BCR and ABL1 were not always observed, and out-of-frame exonic breakpoints in BCR, requiring exon skipping to derive BCR::ABL1, were also noted. Apart from ASXL1 and RUNX1 mutations, extra myeloid gene mutations were mostly present in wild-type cells. We inferred explosive growth attribut

SUBMITTER: Kamizela AE 

PROVIDER: S-EPMC12018454 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature