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

• DOI: 10.1038/335440a0
• Publication Date: 2003-06-12T21:59:33Z
• Authors: David L. Vaux; Suzanne Cory; Jerry M. Adams
• Keywords: 0301 basic medicine; B-Lymphocytes; Cell Survival; Genetic Vectors; Mice, Transgenic; Oncogenes; Flow Cytometry; Hematopoietic Stem Cells; Transfection; Cell Line; 3. Good health; Mice; 03 medical and health sciences; Cell Transformation, Neoplastic; Retroviridae; Proto-Oncogenes; Animals; Interleukin-3; Cell Division

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. By analogy with the translocated c-myc oncogene in other B-lymphoid tumours 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 using a retroviral vector into bone marrow cells from either normal or E mu-myc transgenic mice, in which B-lineage cells constitutively express the c-myc gene. 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). 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.