Quantitative and qualitative impairments in GATA2 and myeloid neoplasms.

GATA2 is a key transcription factor critical for hematopoietic cell development. During the past decade, it became clear that heterozygous germline mutations in the GATA2 gene cause bone marrow failure and primary immunodeficiency syndrome, conditions that lead to a predisposition toward myeloid neoplasms, such as myelodysplastic syndrome, acute myeloid leukemia, and chronic myelomonocytic leukemia. Somatic mutations of the GATA2 gene are also involved in the pathogenesis of myeloid malignancies. Cases with GATA2 gene mutations are divided into two groups, resulting in either a quantitative deficiency or a qualitative defect in the GATA2 protein depending on the mutation position and type. In the former case, GATA2 mRNA expression from the mutant allele is markedly reduced or completely abrogated, and reduced GATA2 protein expression is involved in the pathogenesis. In the latter case, almost equal amounts of structurally abnormal and wildtype GATA2 proteins are predicted to be present and contribute to the pathogenesis. The development of mouse models of these human GATA2-related diseases has been undertaken, which naturally develop myeloid neoplasms.