The Clinical Spectrum, Diagnosis, and Management of GATA2 Deficiency

SIMPLE SUMMARY: A predisposition to myeloid neoplasms has recently been recognized as a defined clinical entity by the World Health Organization. One of the most well-known syndromes within this group is GATA2 deficiency, which is a highly heterogeneous disorder that can include pulmonary and vascular involvement, immunodeficiency, and myeloid neoplasms. The only curative treatment for this syndrome is allogeneic hematopoietic stem cell transplantation (HSCT), which should be performed in patients with GATA2 deficiency before irreversible organ damage. These patients should be referred to a multidisciplinary team to assess all potential and specific organ-system manifestations that could impact the patient’s treatment, and consultations with appropriate subspecialists should be facilitated. Additionally, genetic testing should be offered to first-degree relatives, particularly those considered for donation when an HSCT with a sibling donor is feasible. ABSTRACT: Hereditary myeloid malignancy syndromes (HMMSs) are rare but are becoming increasingly significant in clinical practice. One of the most well-known syndromes within this group is GATA2 deficiency. The GATA2 gene encodes a zinc finger transcription factor essential for normal hematopoiesis. Insufficient expression and function of this gene as a result of germinal mutations underlie distinct clinical presentations, including childhood myelodysplastic syndrome and acute myeloid leukemia, in which the acquisition of additional molecular somatic abnormalities can lead to variable outcomes. The only curative treatment for this syndrome is allogeneic hematopoietic stem cell transplantation, which should be performed before irreversible organ damage happens. In this review, we will examine the structural characteristics of the GATA2 gene, its physiological and pathological functions, how GATA2 genetic mutations contribute to myeloid neoplasms, and other potential clinical manifestations. Finally, we will provide an overview of current therapeutic options, including recent transplantation strategies.