GATA2 Related Conditions and Predisposition to Pediatric Myelodysplastic Syndromes

SIMPLE SUMMARY: GATA2 deficiency is considered one of the most common cancer predisposition syndromes determining myelodysplastic syndrome in children. Little is known of this recently described syndrome, often resulting in a misdiagnosis and unclear management. In this review, we describe GATA2 deficiency clinical presentation in order to focus on phenotypes that, in patients with myelodysplastic syndrome, may be suggestive of GATA2 deficiency. Moreover, due to the lack of clear guidelines, we performed an overview on literature data regarding management of GATA2-related myelodysplastic syndrome, in order to understand the best choice of treatment for these patients. ABSTRACT: Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for a transcriptional regulator of hematopoiesis. The genetic lesion as well as the clinical phenotype are extremely variable; many patients present hematological malignancies, especially MDS with the possibility to evolve into acute myeloid leukemia. Variable immune dysfunction, especially resulting in B- and NK-cell lymphopenia, lead to severe infections, including generalized warts and mycobacterial infection. Defects of alveolar macrophages lead to pulmonary alveolar proteinosis through inadequate clearance of surfactant proteins. Currently, there are no clear guidelines for the monitoring and treatment of patients with GATA2 mutations. In patients with MDS, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) that restores normal hematopoiesis preventing the progression to acute myeloid leukemia and clears long-standing infections. However, to date, the donor type, conditioning regimen, and the optimal time to proceed to HSCT, as well as the level of chimerism needed to reverse the phenotype, remain unclear highlighting the need for consensus guidelines.