Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia

Zhang, B., Ho, Y. W., Huang, Q., Maeda, T., Lin, A., Lee, S.-u., Hair, A., Holyoake, T. L., Huettner, C. and Bhatia, R. (2012) Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia. Cancer Cell, 21(4), pp. 577-592. (doi: 10.1016/j.ccr.2012.02.018) (PMID:22516264) (PMCID:PMC3332001)

Full text not currently available from Enlighten.

Abstract

We characterized leukemia stem cells (LSC) in chronic phase chronic myelogenous leukemia (CML) using a transgenic mouse model. LSC were restricted to cells with long-term hematopoietic stem cell (LTHSC) phenotype. CML LTHSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. Altered cytokine expression in CML BM was associated with selective impairment of normal LTHSC growth and a growth advantage to CML LTHSC. Imatinib (IM) treatment partially corrected abnormalities in cytokine levels and LTHSC growth. These results were validated using human CML samples and provide improved understanding of microenvironmental regulation of normal and leukemic LTHSC and their response to IM in CML.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Holyoake, Professor Tessa and Hair, Dr Alan
Authors: Zhang, B., Ho, Y. W., Huang, Q., Maeda, T., Lin, A., Lee, S.-u., Hair, A., Holyoake, T. L., Huettner, C., and Bhatia, R.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Cell
Publisher:Elsevier
ISSN:1535-6108
ISSN (Online):1878-3686
Published Online:16 April 2012

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
498551Key survival pathways in chronic myeloid leukaemia (cml) stem cells and novel approaches to their eradicationTessa HolyoakeCancer Research UK (CRUK)11008RI CANCER SCIENCES