In this review, we provide an overview of the multilevel regulation of GATA1 protein homeostasis in erythropoiesis and of its deregulation in hematological disease.
Although loss of GATA1 has been known to impair hematopoiesis in animal models for nearly 25 years, the link between GATA1 defects and human blood diseases has only recently been realized.
Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders.
The first three factors, GATAs 1, 2, and 3, are essential for normal hematopoiesis, and their mutations are responsible for a variety of blood disorders.
Therefore, imbalanced gene regulation caused by qualitative and quantitative changes in GATA1 is thought to be involved in specific hematological disease pathogenesis.
Mutations in exon 2 of GATA1 were detected in six of eight DS-AML M7 samples and in four of six DS-TL; no mutation was detected in 13 children with acute lymphoblastic leukemia (DS-ALL), 6 with DS-AML (M0, M2, and M5), 6 with DS-MDS and in 8 DS infants without hematological disorders and 2 children with AML M7 without DS.
Over the past few years, mutations in the gene encoding GATA-1 have been linked to several human hematologic disorders, including X-linked dyserythropoietic anemia and thrombocytopenia, X-linked thrombocytopenia and beta-thalassemia, and Down syndrome acute megakaryoblastic leukemia.
Furthermore, few would have guessed that missense mutations in GATA1 would cause inherited blood disorders, while acquired mutations would be found associated with essentially all cases of acute megakaryoblastic leukemia (AMKL) in children with Down syndrome (DS).