Contribution of aneuploidy to the initiation and progression of childhood B-cell acute lymphoblastic leukemia

Aneuploidy pose deleterious effects on cellular fitness due to important consequences on transcriptome and proteome, leading to reduced proliferation and activation of immune surveillance mechanism. Despite this, aneuploidy is the most frequent genetic abnormality observed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and is the primary oncogenic event arising in utero in hematopoietic precursors. However, the precise role of aneuploidy on leukemia initiation and progression is currently unknown. In here, we aim to study the mechanisms involved on cellular tolerance to aneuploidy in human CD34+ hematopoietic stem/progenitor cells (HSPC), to decipher its contribution to B-ALL initiation. We treated cells with either Reversin or Cytochalasin D, to model random abnormal mitoses or tetraploid intermediates, respectively. HSPCs were followed in vitro and in vivo to assess proliferation, aneuploidy rates, differentiation and karyotype evolution. Our initial results show that aneuploidy is highly detrimental to HSPC and is ultimately lost in competition with their euploid counterparts. In vivo experiments are ongoing to assess whether aneuploidy is tolerated in their own niche.

Publication History

Article published online:
17 May 2022