Abstract
Simple SummaryGATA2 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.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.
Highlights
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders, characterized by cytopenia of one or more hematopoietic lines, ineffective hematopoiesis, and a possible evolution to acute myeloidCancers 2020, 12, 2962; doi:10.3390/cancers12102962 www.mdpi.com/journal/cancersCancers 2020, 12, 2962 leukemia (AML)
The first description of GATA binding protein 2 (GATA2) mutation dates back to 2011, when four independent groups described four clinical phenotypes: Emberger syndrome, MonoMAC syndrome, dendritic cell, monocyte, B and natural killer (NK) lymphoid deficiency (DCML), and familial MDS/AML, all associated with a GATA2 deficiency [3,4,5]
GATA2 mutations were more prevalent in advanced MDS rather than refractory childhood cytopenia; GATA2 mutated patients were older at diagnosis and presented more often with advanced MDS and monosomy 7 compared to GATA2 wild type patients [7]
Summary
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders, characterized by cytopenia of one or more hematopoietic lines, ineffective hematopoiesis, and a possible evolution to acute myeloid. The first description of GATA2 related MDS is due to Scott and colleagues, reporting the first description of GATA2 germline mutation in four MDS/AML families They observed in these families the missense mutations T354M, and the 355delT mutation, absent in 659 healthy controls, such as any other variants of the GATA2 coding sequence. GATA2 mutations were more prevalent in advanced MDS rather than refractory childhood cytopenia; GATA2 mutated patients were older at diagnosis and presented more often with advanced MDS and monosomy 7 compared to GATA2 wild type patients [7] These data have pointed the attention to this unique GATA2 related-MDS, but, even if the comprehension of the disease has progressed, only a few recommendations are available about the best clinical management
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