Activated abl oncogenes and apoptosis: differing responses of transformed myeloid progenitor cell lines

Blood. 1996 May 15;87(10):4368-75.


Activation of the c-abl protooncogene occurs during the generation of both the Abelson murine leukemia virus and the bcrabl fusion gene. To further dissect the biological properties of these proteins, we studied their effect on apoptosis. Using dimethyl sulfoxide (DMSO) to induce apoptosis in the murine myeloid progenitor cell line 32Dcl3, we examined the effect of expression of both v-abl and bcrabl transgenes on apoptosis. v-abl expressing 32Dcl3 cells are sensitive to apoptosis induction, similar to parental 32Dcl3 cells. In contrast, bcrabl expression 32Dcl3 cells are protected from the apoptotic stimulus resulting from DMSO exposure. Analyzing the expression patterns for Bcl-2 and Bax, two proteins known to modulate the apoptotic response, we found a downregulation of Bcl-2 and enhanced expression of Bax in 32Dcl3 cells. In 32Dcl3/v-Abl cells, Bcl-2 expression remained constant while Bax was upregulated, whereas in 32Dcl3 cells expressing bcrabl, there was continuous expression of Bcl-2 at a level greater than observed in v-abl transformed cells. Taken together, our data demonstrate that although both activated abl gene products promote overlapping effects of some biological responses (i.e., factor-independent proliferation) they diverge in their effect on apoptotic signaling pathways.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cell Line, Transformed / drug effects
  • DNA, Neoplasm / analysis
  • Dimethyl Sulfoxide / pharmacology
  • Fusion Proteins, bcr-abl / biosynthesis
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / physiology
  • Gene Expression Regulation, Neoplastic
  • Genes, abl*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Interleukin-3 / pharmacology
  • Mice
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Oncogene Proteins v-abl / biosynthesis
  • Oncogene Proteins v-abl / genetics
  • Oncogene Proteins v-abl / physiology
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • bcl-2-Associated X Protein


  • Bax protein, mouse
  • DNA, Neoplasm
  • Interleukin-3
  • Neoplasm Proteins
  • Oncogene Proteins v-abl
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • bcl-2-Associated X Protein
  • Fusion Proteins, bcr-abl
  • Dimethyl Sulfoxide