Widespread b29 (CD79b) gene defects and loss of expression in chronic lymphocytic leukemia

Alexis A. Thompson*, Ha Nancy Do, Andrew Saxon, Randolph Wall

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Chronic Lymphocytic Leukemia (CLL) is the most prevalent form of leukemia in Western countries, and is characterized by a monoclonal proliferation of primarily immature CD5+ B lymphocytes. The molecular biology of chronic leukemias and lymphomas remains largely unresolved. Surface immunoglobulin (Ig) expression, which is often decreased in CLL, requires the protein product of the B29 gene for translocation of the B cell antigen receptor complex (BCR) to the cell surface and for signal transduction. Because B29 is essential for intracellular assembly and transport of the B cell antigen receptor complex to the cell surface, we postulate that a perturbation in B29 could result in the diminished expression and function of surface Ig in leukemic CLL cells. We have found recurrent aberrations affecting the B29 gene in CLL cells. Analyses of 27 unselected cases of CLL demonstrate that over 75% had low to absent B29 expression which correlated directly to their level of surface Ig expression. Half of these surface B29(low/-) cases had either no or barely detectable levels of B29 mRNA by RNAse protection assay. To date, all of the CLL samples with normal B29 mRNA levels have been found to have point mutations or truncations which would significantly effect the structure and/or function of B29 protein. Strategies directed at correcting these B29 mutations an expected to induce increased Ig surface expression in CLL and may improve the sensitivity of CLL cells to conventional cytotoxic chemotherapy.

Original languageEnglish (US)
Pages (from-to)561-569
Number of pages9
JournalLeukemia and Lymphoma
Volume32
Issue number5-6
DOIs
StatePublished - 1999

Keywords

  • CLL
  • Immunoglobulin
  • Mutations
  • SSCP

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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