Maratheftis Christos I, Bolaraki Pelagia E, Voulgarelis Michael
Department of Pathophysiology, Medical School, National University of Athens, Greece.
Am J Hematol. 2007 Oct;82(10):887-92. doi: 10.1002/ajh.20993.
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.
GATA-1是一种调控红系细胞和巨核细胞生成的转录因子。早期祖细胞中不受阻碍的GATA-1表达使其定向于髓系谱系，引导其向红细胞和巨核细胞分化。骨髓增生异常综合征（MDS）是造血干细胞的克隆性疾病，常表现为红系和/或巨核细胞系发育异常。我们推测，检测不同MDS亚类的造血祖细胞CD34(+)和定向红系细胞CD71(+)中GATA-1的表达水平，可能揭示GATA-1参与该综合征的发病机制。在本研究中，与对照组相比，MDS患者骨髓单个核细胞（BMMCs）、祖细胞CD34(+)和红系细胞CD71(+)中GATA-1 mRNA表达显著升高（P < 0.001）。此外，MDS患者CD71(+)细胞中GATA-1 mRNA表达与其凋亡水平呈正相关（rho = 0.58，P = 0.03）。此外，发现GATA-1表达水平与疾病进展相关。高/INT-2国际预后评分系统（IPSS）风险组的MDS患者，其CD34(+)和CD71(+)细胞中GATA-1 mRNA水平显著高于低/INT-1患者（P < 0.001）。此外，与后者相比，前者CD71(+)细胞凋亡增加，中性粒细胞、血小板数量和血红蛋白水平显著降低。我们得出结论，MDS患者骨髓细胞中GATA-1 mRNA表达增加，高/INT-2患者水平显著更高。红系细胞中较高水平的GATA-1 mRNA与其凋亡程度呈正相关。这些发现表明，GATA-1的上调可能是MDS患者外周血细胞减少的原因。
