Identification of transcriptional targets associated with the expression of p210 Bcr-Abl

Eur J Haematol. 2006 May;76(5):369-83. doi: 10.1111/j.1600-0609.2006.00629.x. Epub 2006 Feb 23.


Objectives: Chronic myeloid leukaemia is caused by the expression of the p210 Bcr-Abl fusion protein which results from the Philadelphia translocation, t(9;22). This oncogene has been the focus of extensive research. However, the molecular mechanisms responsible for the haematological malignancy are not fully understood. The main objective of the current study was to identify novel transcriptional targets of Bcr-Abl.

Methods: In order to achieve this, microarrays were employed in order to conduct a genome-wide expression analysis comparing 32D cells with a transfected clone expressing high levels of p210 Bcr-Abl. Quantitative RT-PCR was employed in order to confirm the observed increase/decrease in expression for a number of the deregulated genes.

Results and conclusions: This comparison identified 138 genes of known function showing altered expression in response to Bcr-Abl-mediated signalling. Among the genes found to be upregulated in response to p210 Bcr-Abl were aldolase 1A and phosphofructokinase, both of which encode key enzymes in the glycolytic pathway. As a consequence of this, we demonstrate that the rate of glycolysis is significantly increased in Bcr-Abl expressing cells in a PI3K-dependent manner. Our results also indicate altered expression of genes involved in cell proliferation, cell adhesion and cell signalling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides
  • Cell Line
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromones / pharmacology
  • Class I Phosphatidylinositol 3-Kinases
  • Clone Cells
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression Profiling*
  • Glycolysis / genetics
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Mice
  • Morpholines / pharmacology
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Piperazines / pharmacology
  • Pyrimidines / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Transcription, Genetic*


  • Benzamides
  • Chromones
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Piperazines
  • Pyrimidines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Imatinib Mesylate
  • 1-phosphatidylinositol 3-kinase p110 subunit, mouse
  • Class I Phosphatidylinositol 3-Kinases
  • Fusion Proteins, bcr-abl