| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
The differentiation inhibitory factor /nm23 protein can inhibit the differentiation of murine and human myeloid leukemia cells. Block of differentiation may be associated with the aggressive behavior of leukemia. To examine the role of nm23 in growth and differentiation of human myeloid leukemia cells, we investigated the relative levels of nm23-H1, nm23-H2 and c-myc transcripts in normal blood cells, normal bone marrow cells, leukemic cell lines, and leukemic cells from patients with acute myeloid leukemia (AML) by reverse transcriptase polymerase chain reaction.
Expression levels of nm23-H1 and nm23-H2 in leukemic cell lines and the AML samples were significantly higher than that in normal blood cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML.An analysis of the correlation between nm23 expression and the clinical parameters demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML,especially in AML-M5.
We confirmed the overexpresion of nm23 proteins in leukemic cells by Western blot, immunohistochemical staining, and flow cytometrical analysis. All leukemic cell lines examined expressed nm23-H1 protein on the cell surface, but the normal blood and bone marrow cells did not. These results show that the cell surface expression of nm23 protein is specific for leukemic cells.
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