Identification of functional defects promoting leukemogenesis in GATA2-deficient individuals

Hematopoiesis is the process in which blood cells are produced by the proliferation of hematopoietic stem and progenitor cells (HSPCs) and their differentiation into the various blood cell subsets. This process is tightly regulated by different co- and transcription factors. Amongst them, GATA2 plays a pivotal role in the proliferation and balance of hematopoietic stem cells (HSCs). Thus, germline GATA2 mutations can disrupt hematopoiesis leading to cytopenia, immunodeficiency or myeloid neoplasia, for instance myelodysplastic syndrome (MDS) or leukemia. Using transgenic mice who are heterozygous in GATA2 (Gata2+/-) in the hematopoietic system, we have previously demonstrated that bone marrow (BM) failure and secondary leukemia can be induced by transplanting Gata2+/- HSPCs into lethally irradiated mice. Interestingly, two weeks after transplantation, HSPC numbers are significantly reduced in the BM of mice who were transplanted with Gata2+/- HSPCs. At later time points, Gata2+/- HSPCs reconstitute the BM of recipients before reaching exhaustion. We now investigate whether, after transplantation, Gata2+/- HSPC numbers decrease due to increased apoptosis or reduced proliferation.

Publication History

Article published online:
17 May 2022