Decreased expression of transcription factor GATA-2 in haematopoietic stem cells in patients with aplastic anaemia.
Aplastic anaemia is characterized by reduced haematopoiesis resulting in pancytopenia. It has been speculated that there is an injury in haematopoietic stem cells in the bone marrow; however, the precise nature of the injury has not been elucidated. In this study, the levels of expression of mRNAs for three transcription factors, GATA-2, SCL and AML1, which function in the early stages of haematopoiesis, were examined by quantitative polymerase chain reaction in patients with aplastic anaemia, idiopathic thrombocytopenic purpura (ITP) and normal subjects. Among these factors, expression of GATA-2 mRNA in purified CD34-positive cells was markedly decreased in aplastic anaemia compared with that in ITP and in normal subjects. The expression levels of SCL and AML1 mRNA in CD34-positive cells in aplastic anaemia were not different from those in normal subjects. When the expression of GATA-2 protein in CD34-positive cells was examined by immunocytochemical analysis, the percentage of GATA-2-positive cells in aplastic anaemia was lower than that in normal subjects. These findings strongly suggest that there is an aberrant expression of transcription factors in stem cells in aplastic anaemia, which may be responsible for the development of the disease.
Fujimaki
S
S
Department of Molecular Diagnostics, Tohoku University School of Medicine, Sendai, Japan.
Harigae
H
H
Sugawara
T
T
Takasawa
N
N
Sasaki
T
T
Kaku
M
M
D000741:Anemia, Aplastic / Q000378:metabolism*; D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D016022:Case-Control Studies; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D005434:Flow Cytometry; D050989:GATA2 Transcription Factor; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics*
D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C494711:GATA2 protein, human; C493728:RUNX1 protein, human; C067143:TAL1 protein, human