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Related Experiment Videos

[BCL-2 gene in lymphocytic malignancy].

M Seto1, K Yamamoto, H Osada

  • 1Laboratory of Chemotherapy, Aichi Cancer Center Research Institute.

Gan to Kagaku Ryoho. Cancer & Chemotherapy
|June 1, 1991
PubMed
Summary
This summary is machine-generated.

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The bcl-2 gene activation by immunoglobulin (Ig) gene fusion in lymphomas leads to extended B cell survival. Malignant transformation requires multiple genetic steps, with bcl-2 rearrangements varying by lymphoma type and geographic location.

Area of Science:

  • Molecular biology
  • Cancer genetics
  • Immunology

Context:

  • The t(14;18) chromosomal translocation activates the bcl-2 gene in certain lymphomas.
  • This translocation results in a fused bcl-2-immunoglobulin (Ig) gene and chimeric mRNA.
  • The bcl-2-Ig fusion does not disrupt the bcl-2 coding frame.

Purpose:

  • To investigate the role of bcl-2 gene rearrangement in lymphoma development.
  • To compare the frequency of bcl-2 involvement in Japanese and American B cell lymphomas and B-cell chronic lymphocytic leukemia (B-CLL).
  • To explore the multistep process required for malignant transformation in bcl-2 activated cells.

Summary:

  • Bcl-2-Ig transgenic mice showed prolonged B cell survival and lymphoproliferation, with some developing diffuse large-cell lymphomas after a latency period.

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  • Malignant transformation in these mice required additional genetic alterations, such as c-myc rearrangement.
  • In Japanese B cell lymphomas, bcl-2 rearrangement frequencies were 31% in follicular lymphoma, 9% in diffuse lymphoma, and 7% in B-CLL.
  • The lower incidence of follicular lymphoma in Japan may be linked to reduced bcl-2 involvement compared to American cases.
  • bcl-2 involvement in B-CLL showed no significant difference between Japan and the U.S.A., with 5' promoter region rearrangements observed in both populations.

    • Impact:

    • Findings suggest that bcl-2 activation is a critical early event but not sufficient for lymphomagenesis, requiring multiple genetic hits.
    • Geographic variations in bcl-2 rearrangement frequencies may contribute to differences in lymphoma incidence.
    • The study highlights the clinical utility of polymerase chain reaction (PCR) for detecting bcl-2 translocations.