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Immunoglobulin Lambda Translocation and Treatment Resistance in Multiple Myeloma

By: Kayci Reyer
Posted: Thursday, May 9, 2019

According to research published in Nature Communications, a specific type of DNA marker, present in 10% of patients with multiple myeloma, may predict a poor prognosis. The marker, a translocation involving the immunoglobulin lambda or IgL locus, may also indicate resistance to standard therapies but is rarely tested for.

“Most patients who have an IgL translocation are actually being diagnosed as having standard-risk disease, so this study has helped explain why some patients who we think will do well end up relapsing,” explained Lawrence H. Boise, PhD, of the Winship Cancer Institute at Emory University, in an Emory press release.

Researchers used the CoMMPass study to analyze structural variants in 795 recently diagnosed patients with multiple myeloma. A total of 10% of patients were found to have some variation of IgL translocation and were more than twice as likely to die within 3 years of their initial diagnosis. Patients in this group did not seem to benefit from immunomodulatory medications such as lenalidomide. Researchers posited that treatment failure in this population may be due to the medication’s targeting of IKZF1, a transcription factor that binds particularly tightly to the IgL gene locus.

Poor prognosis was especially common in patients with specific IgL-MYC translocations. A total of 78% of these translocations occur simultaneously with hyperdiploid disease, which is an indicator of standard risk. This co-occurrence suggests that many cases of IgL-MYC–translocated myeloma may be incorrectly classified.

Additional research is focusing on identifying treatment strategies that may be effective for multiple myelomas carrying IgL translocations. With the support of the Multiple Myeloma Research Foundation, the Winship team is developing a genomic test for the various types of IgL translocations and continuing to validate their study findings.

Disclosure: The study authors reported no conflicts of interest.

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