The role of Bcl-2 in the pathogenesis of B chronic lymphocytic leukemia.
At least three categories of genes are envisaged to be involved in the natural history of B-CLL. First, the genes that are responsible for the transforming event(s) in the (presently unknown) target cell; second, the gene(s) that help the progressive accumulation of malignant cells and finally the gene(s) that cause the progression toward a more aggressive lymphoma. The possibility that the clonal expansion of B-CLL is due to a prolonged life-span of monoclonal B cells rather than to an acceleration of their proliferative activity may now be reinterpreted by taking into account some recent findings on the expression of Bcl-2 gene in B-CLL cells. The Bcl-2 gene product regulates programmed cell death and a number of experiments suggest that Bcl-2 is involved in the selection and maintenance of long-lived memory B cells rescuing them from apoptotic death and leading to their accumulation in the GO phase of the cell cycle. Variant chromosomal translocations have been detected in a small fraction (5-10%) of B-CLL, involving Bcl-2 and the Ig light chain gene. Despite the low percentage of Bcl-2 rearrangements the expression of mRNA and protein is appreciable in most samples of fresh B-CLL cells in an amount comparable to that observed in Karpas 422 cells, which contain a t(14;18).(ABSTRACT TRUNCATED AT 250 WORDS)
Schena
M
M
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Italy.
Gottardi
D
D
Ghia
P
P
Larsson
L G
LG
Carlsson
M
M
Nilsson
K
K
Caligaris-Cappio
F
F
D001402:B-Lymphocytes / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2