LSK derived LSK- cells have a high apoptotic rate related to survival regulation of hematopoietic and leukemic stem cells
A balanced pool of hematopoietic stem cells (HSCs) in bone marrow is tightly regulated, and this regulation is disturbed in hematopoietic malignancies such as chronic myeloid leukemia (CML). The underlying mechanisms are largely unknown. Here we show that the Lin(-)Sca-1(+)c-Kit(-) (LSK(-)) cell pop...
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Published in | PloS one Vol. 7; no. 6; p. e38614 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
04.06.2012
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | A balanced pool of hematopoietic stem cells (HSCs) in bone marrow is tightly regulated, and this regulation is disturbed in hematopoietic malignancies such as chronic myeloid leukemia (CML). The underlying mechanisms are largely unknown. Here we show that the Lin(-)Sca-1(+)c-Kit(-) (LSK(-)) cell population derived from HSC-containing Lin(-)Sca-1(+)c-Kit(+) (LSK) cells has significantly higher numbers of apoptotic cells. Depletion of LSK cells by radiation or the cytotoxic chemical 5-fluorouracil results in an expansion of the LSK(-) population. In contrast, the LSK(-) population is reduced in CML mice, and depletion of leukemia stem cells (LSCs; BCR-ABL-expressing HSCs) by deleting Alox5 or by inhibiting heat shock protein 90 causes an increase in this LSK(-) population. The transition of LSK to LSK(-) cells is controlled by the Icsbp gene and its downstream gene Lyn, and regulation of this cellular transition is critical for the survival of normal LSK cells and LSCs. These results indicate a potential function of the LSK(-) cells in the regulation of LSK cells and LSCs. |
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Bibliography: | Current address: Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, United States of America Current address: Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America Conceived and designed the experiments: CP YC YS HZ ZG DL SL. Performed the experiments: CP YC YS HZ ZG SL. Analyzed the data: CP YC YS HZ ZG DL SL. Contributed reagents/materials/analysis tools: DL. Wrote the paper: SL. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0038614 |