Aplastic anemia is characterized by markedly reduced hemalopoiesis resulting in pancytopenia. It has been speculated that there may be a defect in hematopoietic stem cells in the bone marrow in this disorder, however, the precise nature of the defect has not been elucidated. Several transcription factors are known to function in early stages of hemalopoiesis. Among them, GATA-2, SCL and AML1 have been shown to be indispensable lor early hematopoiesis at the stem cell level by both in vivo and in vitro studies. Thus, it may be possible that expression of these factors might be altered in stem cell diseases which lead to an aberrant proliferation and differentiation of stem cells, and become partly responsible for developing aplastic anemia. In order to examine this question, we evaluated levels of expression of mRNAs for these three transcription factors by quantitative PCR in bone marrow cells, obtained from 17 patients with aplastic anemia, 10 patients with idiopathic thrombocytopenic purpura (1TP) as a disease control, and 10 healthy subjects as normal controls. Among these factors, expression of GATA-2 mRNA in purified CD34 positive cells was markedly decreased in aplastic anemia, compared with that in ITP and in normal controls. Expression levels of SCL and AML1 mRNA in CD34 positive cells were, however, not significantly different from those in ITP and in normal controls. When expression of GATA-2 protein in CD34 positive cells was examined by immunocytochemical analysis, the percentage of GATA-2 positive cells in aplastic anemia was also lower than that in normal controls. In contrast, expression profiles of these factors in ITP were essentially identical to that in normal controls. These findings strongly suggest that there is an aberrant expression of GATA-2 in stem cells in aplastic anemia, which may be responsible for the development of the disease.
|Issue number||11 PART II|
|Publication status||Published - 2000 Dec 1|
ASJC Scopus subject areas
- Cell Biology