A study, published recently in Clinical Cancer Research, has found that myeloma patients may be genetically predisposed to Velcade-induced peripheral neuropathy. Researchers carried out a genome-wide association study (GWAS) of over 370,000 single nucleotide polymorphisms (SNPs) in 469 myeloma patients treated with Velcade and dexamethasone prior to high-dose therapy and autologous stem cell transplantation in several Intergroupe Francophone du Myelome (IFM)-run trials. A novel candidate genetic locus mapping to the PKNOX1 gene and, in the immediate vicinity, the CBS gene at 21q22.3 were associated with severe Velcade-induced toxicity. These results not only shed light on the neurotoxic mechanisms of Velcade-induced neuropathy but also potentially provide new targets for neuroprotective strategies.

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