GATA1 insufficiencies in dysmegakaryopoiesis of myelodysplastic syndromes

Abstract

GATA1 is one of critical transcription factors for megakaryopoiesis and platelet production. Our study aimed to explore the correlations between GATA1 expression and dysmegakaryopoiesis in myelodysplastic syndromes (MDS). Data of blood cell counts, cytogenetics and TP53 mutation status from 90 MDS patients at diagnosis were collected. Firstly, we assessed GATA1 expression level of megakaryocytes by performing immunohistochemical staining on paraffin-embedded bone marrow biopsy sections from these patients. According to GATA1 expression level of megakaryocytes and positive megakaryocyte percentage, we assigned each patient a GATA1 score. Compared with TP53-wildtype patients, GATA1 scores significantly decreased in TP53-mutated patients (P < 0.001). Patients with abnormal karyotypes showed decreased GATA1 scores than those with normal karyotypes (P = 0.024). GATA1 expression levels were significantly downregulated in dysplastic megakaryocytes, especially micromegakaryocytes, compared with normal megakaryocytes (P < 0.001). Furthermore, we explored the correlation between GATA1 expression levels and cytogenetic abnormalities of the same megakaryocyte using the morphology antibody chromosome (MAC) technique on fresh bone marrow smears. We found that GATA1-negative megakaryocytes had higher frequencies of cytogenetic abnormalities. Our results indicated that decreased GATA1 expression level of megakaryocytes was significantly associated with TP53 mutations, abnormal karyotypes and dysmegakaryopoiesis in MDS, suggesting that downregulation of GATA1 expression levels of megakaryocytes plays a critical role in the pathogenesis of MDS.