Abstract
High dose-rate radiation is known to induce acute myeloid leukemia (AML) in human and mice. Recent reports suggest that cancer stem cells initiate and maintain cancer tissue. In this study, we analyzed cell-surface antigen of murine radiation-induced AMLs, to identify the initiation and differentiation stages of AMLs. Eight AMLs were induced in male C3H/He Nrs mice by 3Gy of gamma-ray at a dose rate of 1.0 Gy/min. Spleen cells from each mouse with AML were injected into syngeneic mice. Bone marrows and spleens of recipient mice were analyzed for the cell-surface antigens by flowcytometry. The analysis of initiation and differentiation stage revealed that 4 out of 8 AMLs had an increased cell-population of common myeloid progenitor (CMP)-like cells, and the remaining 4 AMLs were rich in hematopoietic stem cell (HSC)-like cells. All AMLs had similar cellular composites both in the bone marrow and the spleen. Partial losses of chromosome 2 were detected in 2 of 4 CMP-like AMLs by array CGH analysis. Furthermore, we transplanted each of HSC-, CMP- and common lymphoid progenitor (CLP)-like cells separated from a CMP-like AMLs into syngeneic mice. It was shown that the development of AMLs from transplanted CLP-like cells was suppressed or delayed compared to those from HSC- or CMP-like cells. The results indicate that murine radiation-induced AMLs with the partial loss of chromosome 2 were initiated from HSC or CMP, transforming into AML stem cells. This work was supported by a grant from Aomori Prefecture, Ja
