|Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
The self-renewal and differentiation of hematopoietic progenitors are regulated by the interaction between Notch receptors and Notch ligands. Since acute myeloblastic leukemia (AML) originates from dysregulated hematopoietic progenitors, we thought that some abnormalities in the Notch system might be involved in the abnormal proliferation of AML cells. Furthermore, we thought that the expression of Notch protein might be one of the prognostic factors of the patients. Firstly, we found that most of the AML cell lines and half of the primary AML cells from patients expressed Notch-1 protein. Some samples showed a fragment which appeared to be a constitutively active form or an aberrant sized fragment. Other samples expressed the Notch ligand protein such as Jagged 1. Secondly, we established a novel human AML cell line, TMD7, of which growth was stimulated by Notch ligands. Thirdly, we examined the effects of recombinant Notch ligand proteins on in vitro growth of AML cells. For TMD7 cells, the Notch ligand promoted the short-term growth, however, suppressed the self-renewal capacity and long-term growth. For another cell line, Notch ligand protein suppressed the growth and self-renewal capacity while inducing differentiation into macrophage-like cells. We additionally found that Notch ligands needed to be immobilized on culture wells to affect the cells. At present, we are examining the effects of the Notch ligands on the growth of primary AML cells from patients. Until now, we have not found the clear relationship between the prognosis of the patients and the expression of Notch proteins.