The most frequent primary abnormalities in multiple myeloma (MM) are trisomies of odd-numbered chromosomes or translocations involving the immunglobulin heavy chain (IGH) gene locus. The most common MM-associated IGH translocations are t(11;14), t(4;14), t(6;14), t(14;16) and t(14;20) in the order of their occurrence. The consequence of these rearrangements is the dysregulation of genes juxtaposed to transcriptional enhancers in the IGH locus. Prognosis and risk stratification strongly depend on the detection and interpretation of cytogenetic primary abnormalities. t(14;16) and t(14;20) are considered as high risk, t(4;14) as intermediate risk and t(6;14) and t(11;14) as standard risk cytogenetic aberrations in patients with MM based on FISH testing. Secondary aberrations are also influencing the outcome.
MAF overexpression caused by t(14;16)(q32;q23) increases gene expression levels of the downstream target genes cyclin D2 and integrin beta 7 and contributes to the pathogenesis of MM by at least two mechanisms. Cyclin D2 is a major player in cell cycle regulation and Cyclin D2 dysregulation promotes tumor development. Furthermore, overexpression of integrin beta 7 affects the interaction between myeloma cells and bone marrow stroma and thus promotes transformation of malignant plasma cells.
Clinical Applications
- Multiple Myeloma and Plasma Cell Neoplasms (MM)