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 (r = 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. Am. J. Hematol. 82:887-892, 2007.

Derepression of the DNA Methylation Machinery of the Gata1 Gene Triggers the Differentiation Cue for Erythropoiesis

“…Increased apoptotic death of CD34 ϩ hematopoietic progenitors has been assumed to be one of the mechanisms underlying the hematopoietic defect in early-stage MDS patients (39). One clinical report found that GATA1 mRNA expression had increased approximately 10-fold in the CD34 ϩ progenitors of MDS patients (40). In this study, we found that ectopic increases of GATA1 expression in HSCs led them to apoptosis and subsequent depletion.…”

GATA-1 and GATA-2 binding to 3′ enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines

“…In our results, increase of GATA-1 mRNA was observed from stem cell fraction to progenitor cell fraction. Furthermore, Maratheftis et al 33 reported the upregulation of GATA-1 mRNA of CD34 þ cells in myelodysplastic syndrome compared with that of normal control.…”

Iron Chelation Improves Ineffective Erythropoiesis and Iron Overload in Myelodysplastic Syndrome Mice

“…While GATA1 is as an important transcriptional regulator in normal erythropoiesis [36], BCL-xl is implicated in the anti-apoptosis effect of EPO on erythroblasts [37]. Aberrant GATA1 expression in MDS have been described with evidence of increased GATA1 expression in bone marrow CD34+ stem and progenitor cells as well as CD71+ erythroblasts from MDS patients [38]. Furthermore, normal upregulation of GATA1 and BCL-xl during human erythroid differentiation is lost in MDS [39].…”