Guerrasio A, Saglio G, Rosso C, Alfarano A, Camaschella C, Lo Coco F, Biondi A, Rambaldi A, Nicolis S, Ottolenghi S
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Italy.
Leukemia. 1994 Jun;8(6):1034-8.
Expression of the transcription factor GATA-1, which regulates several erythroid specific genes and possibly also some megakaryocytic genes, has been previously detected in normal erythroblasts, megakaryocytes, and basophils, and in some myeloid cell lines. It has been suggested that GATA-1 may be first expressed in a common progenitor and then further activated during erythroid-megakaryocytic and basophilic differentiation and repressed during myeloid maturation. We investigated GATA-1 mRNA expression in highly purified leukemic blasts representing different lineages and stages of myeloid differentiation and in a recently established leukemic cell line, GF-D8, which exhibits morphological, cytochemical and immunophenotypic characteristics of early myeloid progenitor cells. We found GATA-1 expression in five of five myeloid and in one megakaryocytic blast crisis of CML, in four of six cases of myelomonocytic leukemias (M4 according to FAB classification), in one case of erythroleukemia (M6), whereas lymphoid blast crisis of CML and all other FAB groups were completely negative. In addition, a low level of GATA-1 mRNA was also expressed by the GF-D8 cell line. These data further support the hypothesis that GATA-1 expression may occur not only in erythroid and megakaryocytic progenitors, but also in early myeloid progenitors, and then be further regulated during lineage-specific maturation.
转录因子GATA-1可调控多个红系特异性基因,也可能调控一些巨核细胞基因。此前已在正常成红细胞、巨核细胞、嗜碱性粒细胞以及某些髓系细胞系中检测到该因子的表达。有人提出,GATA-1可能首先在一个共同祖细胞中表达,然后在红系-巨核细胞系和嗜碱性细胞分化过程中进一步激活,而在髓系成熟过程中受到抑制。我们研究了高度纯化的代表髓系分化不同谱系和阶段的白血病原始细胞以及最近建立的白血病细胞系GF-D8中GATA-1 mRNA的表达,GF-D8表现出早期髓系祖细胞的形态、细胞化学和免疫表型特征。我们发现,在5例髓系白血病原始细胞和1例慢性粒细胞白血病巨核细胞急变中、6例粒单核细胞白血病(根据FAB分类为M4)中的4例、1例红白血病(M6)中检测到GATA-1表达,而慢性粒细胞白血病淋巴细胞急变和所有其他FAB组均完全阴性。此外,GF-D8细胞系也表达低水平的GATA-1 mRNA。这些数据进一步支持了以下假说:GATA-1不仅可能在红系和巨核细胞祖细胞中表达,也可能在早期髓系祖细胞中表达,然后在谱系特异性成熟过程中受到进一步调控。