期刊
BLOOD
卷 129, 期 12, 页码 1577-1585出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2016-10-696054
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资金
- CJ Martin Overseas Biomedical Research Fellowship (National Health and Medical Research Council, Australia)
- New York Stem Cell Foundation
- National Institutes of Health National Cancer Institute [R01CA188055]
Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research.
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