期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 121, 期 1, 页码 384-395出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI41495
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资金
- United States Veterans Administration
- Sanofi Aventis
- NIH [KO1 CA 129151 01, K12CA07693]
- St Baldric's Foundation
- ASCO
- NATIONAL CANCER INSTITUTE [F32CA007693, K01CA129151] Funding Source: NIH RePORTER
Human leukemic stem cells, like other cancer stem cells, are hypothesized to be rare, capable of incomplete differentiation, and restricted to a phenotype associated with early hematopoietic progenitors or stem cells However, recent work in other types of tumors has challenged the cancer stem cell model Using a robust model of xenotransplantation based on NOD/SCID/IL2R gamma c-deficient mice, we confirmed that human leukemic stem cells, functionally defined by us as SCID leukemia-initiating cells (SL-ICs), are rare in acute myelogenous leukemia (AML) In contrast to previous results, SL-ICs were found among cells expressing lineage markers (i e, among Lin(+) cells), CD38, or CD45RA, all markers associated with normal committed progenitors Remarkably, each engrafting fraction consistently recapitulated the original phenotypic diversity of the primary AML specimen and contained self-renewing leukemic stem cells, as demonstrated by secondary transplants While SL-ICs were enriched in the Lm(-)CD38(-) fraction compared with the other fractions analyzed, SL-ICs in this fraction represented only one-third of all SL-ICs present in the unfractionated specimen These results indicate that human AML stem cells are rare and enriched but not restricted to the phenotype associated with normal primitive hematopoietic cells These results suggest a plasticity of the cancer stem cell phenotype that we believe has not been previously described
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