High ALDHdim-expressing CD34+CD38- cells in leukapheresed peripheral blood is a reliable guide for a successful leukemic xenograft model of acute myeloid leukemia

The primary human acute myeloid leukemia (AML) cell injection xenograft mouse model is used to investigate multimodal therapies and drug screening on tumor growth. Since xenograft models using human cell lines to examine drug response are not correlated with the clinical outcomes observed in patients, a xenograft model using primary human cells has been used as a more appropriate model with which to minimize this problem. Although bone marrow (BM) cells from patients are often regarded as superior sources to establish xenograft models due to the high frequency of stem cell populations, there is a fatal drawback; only small volumes can be obtained and used for the generation of the leukemic xenograft model. Indeed, longevity of AML characteristics, as well as sufficient stem cells in the xenograft model, should be guaranteed to analyze the therapeutic response to a drug. Therefore, we examined whether leukapheresed peripheral blood (LPB) consists of reliable leukemic stem cells (LSCs) and ALDH(dim)-expressing CD34(+)CD38(-) cells, and functions in grafting human AML with virulence compared to that of BM. LPB cells showed an advantage for the xenograft mouse model with AML cell homing, engraftment and a high human ALDH(dim)-expressing CD34(+)CD38(-) cell population, suggesting an alternative cell source to BM. Overall, this xenograft model using LPB offers the possibility of overcoming the small volume limitation of BM and prevents individual variation by using a single LPB sample. This result is noteworthy in identifying cell sources capable of generating a stable xenograft model.