PubMed ID

22675576

UMMS Affiliation

Department of Medicine, Division of Hematology/Oncology

Date

6-4-2012

Document Type

Article

Subjects

Bone Marrow Cells; Hematopoietic Stem Cells

Disciplines

Cancer Biology | Cell and Developmental Biology | Hematology | Life Sciences | Medicine and Health Sciences

Abstract

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.

Comments

Citation: Peng C, Chen Y, Shan Y, Zhang H, Guo Z, et al. (2012) LSK Derived LSK Cells Have a High Apoptotic Rate Related to Survival Regulation of Hematopoietic and Leukemic Stem Cells. PLoS ONE 7(6): e38614. doi:10.1371/journal.pone.0038614. Link to article on publisher's site

Copyright: © 2012 Peng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources

Link to Article in PubMed