GATA‐1 transcription factor is up‐regulated in bone marrow hematopoietic progenitor CD34+ and erythroid CD71+ cells in myelodysplastic syndromes

Abstract

GATA-1 is a transcription factor governing the production of erythroid and megakaryocytic cells. Unobstructed GATA-1 expression in early progenitor cells commits them to the myeloid lineage, channeling its differentiation towards erythrocytes and megakaryocytes. Myelodysplastic Syndromes (MDS) are clonal disorders of the hematopoietic stem cell frequently presenting dysplasia in erythroid and/or megakaryocytic lineage. We reasoned that measurement of GATA-1 expression levels in hematopoietic progenitor CD34(+) and the committed erythroid CD71(+) cells, from various MDS subcategories, could demonstrate GATA-1 involvement in the pathogenesis of the syndrome. In this study, MDS patients displayed significantly elevated GATA-1 mRNA expression, in bone marrow mononuclear cells (BMMCs), progenitor CD34(+) and erythroid CD71(+) cells in contrast to the control population (P < 0.001). Additionally, GATA-1 mRNA expression in MDS CD71(+) cells was positively correlated with their apoptotic levels (rho = 0.58, P = 0.03). Furthermore, GATA-1 expression levels were found to correlate with the disease progression. MDS patients in high/INT-2 IPSS risk group expressed significantly higher GATA-1 mRNA levels, in both CD34(+) and CD71(+) cells, as opposed to low/INT-1 patients (P < 0.001). Moreover, the former displayed increased apoptosis in the CD71(+) cells and significantly reduced neutrophil and platelet numbers and hemoglobin levels compared with the latter. We conclude that MDS patients display an increase of GATA-1 mRNA expression in BM cells, with high/INT-2 patients showing significantly higher levels. The higher level of GATA-1 mRNA in erythroid cells was positively correlated with their degree of apoptosis. These findings suggest that the up-regulation of GATA-1 may be responsible for the peripheral cytopenias in MDS.