A potential role for centrosomal deregulation within IgH translocation-positive myeloma

Multiple myeloma is a late stage B-cell malignancy that is characterized by recurrent translocations into the immunoglobulin heavy chain locus as well as multiple and complex chromosomal abnormalities. Multiple myeloma is not characterized by a defining IgH translocation partner locus; rather, the frequency of individual translocations ranges from 5% to 15% of the patient population. The current hypothesis that IgH translocations contribute to chromosomal instability through the augmented expression of cyclin D family members and upstream regulatory gene products has led to the development of clinical therapies targeting these potentially oncogenic gene products. Here, we postulate that IgH translocations affect both cyclin D family members and spindle assembly pathways. In forming the hypothesis, this manuscript provides a mechanistic connectivity between IgH translocations and associated chromosome 13 deletions and highlights a number of additional gene products that, along with already defined target genes, may be deregulated in myeloma and represent potential therapeutic targets.