Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region.
Document Type
Article
Publication Date
2007
Keywords
Apoptosis, Bone-Marrow, Cell-Division, Drug-Resistance-Neoplasm, Gene-Expression-Profiling, Humans, Leukemia-Myeloid-Acute, Mice, Mice-Mutant-Strains, Models-Biological, Neoplasm-Transplantation, Neoplastic-Stem-Cells, Osteoblasts
First Page
1315
Last Page
1321
JAX Source
Nat Biotechnol 2007 Nov; 25(11):1315-21.
Abstract
Acute myelogenous leukemia (AML) is the most common adult leukemia, characterized by the clonal expansion of immature myeloblasts initiating from rare leukemic stem (LS) cells. To understand the functional properties of human LS cells, we developed a primary human AML xenotransplantation model using newborn nonobese diabetic/severe combined immunodeficient/interleukin (NOD/SCID/IL)2r gamma(null) mice carrying a complete null mutation of the cytokine gamma c upon the SCID background. Using this model, we demonstrated that LS cells exclusively recapitulate AML and retain self-renewal capacity in vivo. They home to and engraft within the osteoblast-rich area of the bone marrow, where AML cells are protected from chemotherapy-induced apoptosis. Quiescence of human LS cells may be a mechanism underlying resistance to cell cycle-dependent cytotoxic therapy. Global transcriptional profiling identified LS cell-specific transcripts that are stable through serial transplantation. These results indicate the potential utility of this AML xenograft model in the development of novel therapeutic strategies targeted at LS cells.
Recommended Citation
Ishikawa F,
Yoshida S,
Saito Y,
Hijikata A,
Fukata M,
Miyamoto T,
Lyons B,
Ohshima K,
Akashi K,
Harada M,
Shultz LD,
et a.
Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol 2007 Nov; 25(11):1315-21.