The role of bcl-2 in the pathogenesis of b chronic lymphocytic leukemia

Marina Schena, Daniela Gottardi, Paolo Ghia, Lars Gunnar Larsson, Mats Carlsson, Kenneth Nilsson, Federico Caligaris-Cappio

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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;lS). Southern blot analysis of 16 B-CLL cases with high expression of Bcl-2 failed to reveal both gene amplification and rearrangement, thereby suggesting that the level of Bcl-2 expression in B-CLL does not reflect a rearrangement of Bcl-2 gene, which appears to be a rare event in CLL cells. In addition, the half life of Bcl-2 mRNA is not prolonged in CLL cells. The expression of Bcl-2 mRNA can be modulated in B-CLL cells by using B cell activators and cytokines. In the transition from a resting to a cycling phase, Bcl-2 expression is downregulated indicating that proliferation and Bcl-2 expression are inversely related in malignant B-CLL cells from peripheral blood as observed for normal B lymphocytes derived from secondary follicles. By culturing B-CLL cells in the presence of an antisense phosphorothioate oligodeoxynucleotide complementary to the translation-initiation site of Bcl-2 gene, DNA fragmentation, characteristic of apoptosis, can be seen in a proportion of cases. These data lead to the plausible hypothesis that the high Bcl-2 expression in B-CLL cells might confer on them a survival advantage favouring their relentless accumulation, perhaps by inhibition of apoptosis.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalLeukemia and Lymphoma
Volume11
Issue number3-4
DOIs
Publication statusPublished - 1993

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
bcl-2 Genes
B-Lymphocytes
Messenger RNA
Genes
Apoptosis
Genetic Translocation
Gene Rearrangement
Gene Amplification
Oligodeoxyribonucleotides
DNA Fragmentation
Southern Blotting
Natural History
Oncogenes
Half-Life
Lymphoma
Blood Cells
Cell Cycle
Cell Death
Down-Regulation

Keywords

  • B-chronic lymphocytic leukemia
  • B-CLL
  • Bcl 2

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Schena, M., Gottardi, D., Ghia, P., Larsson, L. G., Carlsson, M., Nilsson, K., & Caligaris-Cappio, F. (1993). The role of bcl-2 in the pathogenesis of b chronic lymphocytic leukemia. Leukemia and Lymphoma, 11(3-4), 173-179. https://doi.org/10.3109/10428199309086993

The role of bcl-2 in the pathogenesis of b chronic lymphocytic leukemia. / Schena, Marina; Gottardi, Daniela; Ghia, Paolo; Larsson, Lars Gunnar; Carlsson, Mats; Nilsson, Kenneth; Caligaris-Cappio, Federico.

In: Leukemia and Lymphoma, Vol. 11, No. 3-4, 1993, p. 173-179.

Research output: Contribution to journalArticle

Schena, M, Gottardi, D, Ghia, P, Larsson, LG, Carlsson, M, Nilsson, K & Caligaris-Cappio, F 1993, 'The role of bcl-2 in the pathogenesis of b chronic lymphocytic leukemia', Leukemia and Lymphoma, vol. 11, no. 3-4, pp. 173-179. https://doi.org/10.3109/10428199309086993
Schena, Marina ; Gottardi, Daniela ; Ghia, Paolo ; Larsson, Lars Gunnar ; Carlsson, Mats ; Nilsson, Kenneth ; Caligaris-Cappio, Federico. / The role of bcl-2 in the pathogenesis of b chronic lymphocytic leukemia. In: Leukemia and Lymphoma. 1993 ; Vol. 11, No. 3-4. pp. 173-179.
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