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Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells

Abstract

A common feature of follicular lymphoma, the most prevalent haematological malignancy in humans, is a chromosome translocation (t(14;18)) that has coupled the immunoglobulin heavy chain locus to a chromosome 18 gene denoted bcl-2 (refs 1–6). By analogy with the translocated c-myc oncogene in other B-lymphoid tumours (reviewed in ref. 7), bcl-2 is a candidate oncogene, but no biological effects of bcl-2 have yet been reported. To test whether bcl-2 influences the growth of haematopoietic cells, either alone or together with a deregulated c-myc gene, we have introduced a human bcl-2 complementary DNA (ref. 3) using a retroviral vector into bone marrow cells from either normal or Eµ-myc transgenic mice, in which B-lineage cells constitutively express the c-myc gene8–10. Bcl-2 cooperated with c-myc to promote proliferation of B-cell precursors, some of which became tumorigenic. To determine how bcl-2 expression impinges on growth factor requirements, the gene was introduced into a lymphoid and a myeloid cell line that require interleukin 3 (IL-3) (refs 11 and 12). In the absence of IL-3, bcl-2 promoted the survival of the infected cells but they persisted in a G0 state, rather than proliferating. These results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.

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Vaux, D., Cory, S. & Adams, J. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335, 440–442 (1988). https://doi.org/10.1038/335440a0

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