Chronic myeloid leukemia stem cells display alterations in expression of genes involved in oxidative phosphorylation

Flis, K., Irvine, D., Copland, M. , Bhatia, R. and Skorski, T. (2012) Chronic myeloid leukemia stem cells display alterations in expression of genes involved in oxidative phosphorylation. Leukemia and Lymphoma, 53(12), pp. 2474-2478. (doi:10.3109/10428194.2012.696313)

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Publisher's URL: http://dx.doi.org/10.3109/10428194.2012.696313

Abstract

The mitochondrial respiratory chain (MRC) consists of protein complexes I, II, III, IV and V that support oxidative phosphorylation (OXPHOS), which depends on electron transport to generate adenosine triphosphate (ATP). Electron “leakage” from the MRC generates reactive oxygen species (ROS). Chronic myeloid leukemia in chronic phase (CML-CP) stem cells (LSCs) produce high levels of mitochondrial ROS, causing oxidative DNA damage, resulting in genomic instability, generating imatinib-resistant BCR–ABL1 kinase mutants and additional chromosomal aberrations. Using global mRNA microarray analysis combined with Ingenuity Pathway Analysis we found that LSCs display enhanced expression of genes encoding MRC complexes I, II, IV and V. However, expression of genes encoding complex III was deregulated. Treatment with imatinib did not correct the aberrant levels of MRC genes. Therefore we postulate that abnormal expression of MRC genes may facilitate electron “leakage” to promote the production of ROS and accumulation of genomic instability in LSCs in imatinib-naive and imatinib-treated patients.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Irvine, Dr David and Copland, Professor Mhairi
Authors: Flis, K., Irvine, D., Copland, M., Bhatia, R., and Skorski, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Leukemia and Lymphoma
ISSN:1042-8194
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
506531An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandScottish Executive Health Department (SEHHD-CSO)SCD/04RI CANCER SCIENCES
506532An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandLeukaemia & Lymphoma Research (LRF)11017RI CANCER SCIENCES
354131Novel drug combinations for eradication of Ph+/Bcr-Abl+ haemopoietic stem cells in chronic myeloid leukaemia (CML)Mhairi CoplandMedical Research Council (MRC)G84/6317RI CANCER SCIENCES