The role of GATA2 in adult hematopoiesis and cell fate determination

Abstract

The correct maintenance and differentiation of hematopoietic stem cells (HSC) in bone marrow is vital for the maintenance and operation of the human blood system. GATA2 plays a critical role in the maintenance of HSCs and the specification of HSCs into the different hematopoietic lineages, highlighted by the various defects observed in patients with heterozygous mutations in GATA2, resulting in cytopenias, bone marrow failure and increased chance of myeloid malignancy, termed GATA2 deficiency syndrome. Despite this, the mechanisms underlying GATA2 deficiency syndrome remain to be elucidated. The detailed description of how GATA2 regulates HSC maintenance and blood lineage determination is crucial to unravel the pathogenesis of GATA2 deficiency syndrome. In this review, we summarize current advances in elucidating the role of GATA2 in hematopoietic cell fate determination and discuss the challenges of modeling GATA2 deficiency syndrome.

Novel insights into the ontogeny of basophils

“…GATA2 deficiency syndrome is caused by heterozygous and loss-of-function mutation in GATA2 and displays severe abnormalities in multiple myeloid and lymphoid lineages, including monocytopenia, neutropenia, and dendritic cell deficiency ( 95 ). Moreover, patients with GATA2 deficiency syndrome develop myeloid neoplasms, including myelodysplastic syndrome and acute myeloid leukemia, with a median age of onset at 17 years.…”

“…When the CEBPA +39-kb enhancer region is mutated in human hematopoietic progenitor cells, the differentiation into basophils is partially blocked, but the differentiation into mast cells is rather enhanced (94), possibly through reduced CEBPA expression. GATA2 deficiency syndrome is caused by heterozygous and loss-of-function mutation in GATA2 and displays severe abnormalities in multiple myeloid and lymphoid lineages, including monocytopenia, neutropenia, and dendritic cell deficiency (95). Moreover, patients with GATA2 deficiency syndrome develop myeloid neoplasms, including myelodysplastic syndrome and acute myeloid leukemia, with a median age of onset at 17 years.…”