Transcription Factors GATA1/2 in Hematological Disorders

GATA1 and GATA2 are zinc-finger transcription factors essential for normal hematopoiesis. As genetic testing becomes more widely integrated into clinical practice, GATA1/2-related disorders are increasingly recognized, making it important for clinicians to understand their diagnosis and management.

This review summarizes the clinical features, disease mechanisms, and management considerations for GATA1- and GATA2-related hematological disorders.

We discuss germline GATA1 mutations causing rare X-linked erythroid and megakaryocytic cytopenias, somatic GATA1 mutations driving myeloid leukemia of Down syndrome, and germline GATA2 mutations causing GATA2 deficiency syndrome-a predisposition to immunodeficiency and myeloid malignancies affecting up to 75%-80% of carriers. Evolving genotype-phenotype patterns, the somatic mutational landscape, and current therapeutic strategies, including allogeneic hematopoietic stem cell transplantation (HSCT), are reviewed.

Despite growing recognition of GATA1/2-related disorders, many aspects of disease biology and clinical variability remain incompletely understood. Earlier identification and risk stratification of affected patients, along with advances in transplant approaches and novel therapeutics, will be essential for improving outcomes.

The authors have confirmed clinical trial registration is not needed for this submission.