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Decoupling Of Normal Cd40/Interleukin-4 Immunoglobulin Heavy Chain Switch Signal Leads To Genomic Instability In Sgh-Mm5 And Rpmi 8226 Multiple Myeloma Cell Lines, William Y.K Hwang, Charles A. Gullo Phd, Jie Shen, Chee Kok Poh, S. C. Tham, G. Cow, M. Au, E. W. E. Chan, G. Teoh
Decoupling Of Normal Cd40/Interleukin-4 Immunoglobulin Heavy Chain Switch Signal Leads To Genomic Instability In Sgh-Mm5 And Rpmi 8226 Multiple Myeloma Cell Lines, William Y.K Hwang, Charles A. Gullo Phd, Jie Shen, Chee Kok Poh, S. C. Tham, G. Cow, M. Au, E. W. E. Chan, G. Teoh
Charles Gullo
The processes mediating genomic instability and clonal evolution are obscure in multiple myeloma (MM). Acquisition of new chromosomal translocations into the switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in MM, often heralds transformation to more aggressive disease. Since the combined effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch recombination (CSR), and this process involves DNA double strand break repair (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this study, we show that MM cell lines that …