Description

• Title:
  Chronic myeloid leukemia stem cells display alterations in expression of genes involved in oxidative phosphorylation.
• Creator:
  Flis, Krzysztof;
  Irvine, David;
  Copland, Mhairi;
  Bhatia, Ravi;
  Skorski, Tomasz
• Description:
  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.
• Object availability:
  free access
• Date:
  2012.12
• Type:
  Article;
  PeerReviewed
• Language:
  English
• Format:
  application/pdf
• Relation: http://eprints.ibb.waw.pl/389 ;doi: 10.3109/10428194.2012.696313
• Subject:
  QH Natural history;
  QH426 Genetics;
  QP Physiology;
  R Medicine (General)
• Identifier: http://eprints.ibb.waw.pl/389/1/KFLIS2012_Leukemia_and_Lymphoma_-_revised_manuscript.pdf ;
  Flis, Krzysztof and Irvine, David and Copland, Mhairi and Bhatia, Ravi and Skorski, Tomasz (2012) Chronic myeloid leukemia stem cells display alterations in expression of genes involved in oxidative phosphorylation. Leukemia & lymphoma, 53 (12). pp. 2474-8. ISSN 1029-2403
• Data provider:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
• Can I use it?:
  seek permission
• Type:
  other