Novel Primitive Lymphoid Tumours Induced in Transgenic Mice by Cooperation Between Myc and bcl-2

Nature. 1990 Nov 22;348(6299):331-3. doi: 10.1038/348331a0.

Abstract

The putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas. The bcl-2 gene product is not altered by the translocation, but its expression is deregulated, presumably by the Igh enhancer E mu. Constitutive bcl-2 expression seems to augment cell survival, as infection with a bcl-2 retrovirus enables certain growth factor-dependent mouse cell lines to maintain viability when deprived of factor. Furthermore, high levels of the bcl-2 product can protect human B and T lymphoblasts under stress and thereby confer a growth advantage. Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro but do not show a propensity for spontaneous tumorigenesis. In contrast, an analogous myc transgene, designed to mimic the myc-Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells. Previous experiments have suggested that bcl-2 can cooperate with deregulated myc to improve in vitro growth of pre-B and B cells. Here we describe a marked synergy between bcl-2 and myc in doubly transgenic mice. E mu-bcl-2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than E mu-myc mice. Suprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Cell Line
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 18
  • Genes, myc*
  • Humans
  • Leukocytes / cytology
  • Lymphoma / genetics*
  • Mice
  • Mice, Transgenic
  • Oncogenes*
  • Phenotype
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2
  • Translocation, Genetic

Substances

  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2