BCR/ABL confers growth factor independence upon a murine myeloid cell line

Leukemia. 1992 Aug;6(8):796-800.

Abstract

The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes, BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines. To investigate the ability of BCR/ABL to generate growth factor independence in myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54 and A74 were capable of IL-3 independent growth and tumor formation in syngeneic mice. Relief of growth factor dependence was not mediated by autocrine release of IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant constitutive expression of c-myc, c-jun, and c-fos was observed in the p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL transformation and relief of IL-3 dependence involve not only pathways that can substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also pathways that recruit constitutive c-jun and c-fos expression.

Publication types

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

MeSH terms

  • Animals
  • Cell Division / genetics
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic
  • Gene Expression
  • Genes, fos / genetics
  • Genes, jun / genetics
  • Genes, myc / genetics
  • Hematopoietic Stem Cells / physiology*
  • Interleukin-3 / physiology
  • Mice
  • Oncogenes / physiology*
  • Poly A / analysis
  • RNA / analysis
  • RNA, Messenger
  • Signal Transduction

Substances

  • Interleukin-3
  • RNA, Messenger
  • Poly A
  • RNA