03 May 2019

A new DNA marker may prove useful as a predictor of poor outcomes in multiple myeloma, US researchers have reported.

20% of multiple myeloma patients relapse or die within two years of diagnosis, and are designated ‘high-risk’. Scientists at Emory University, Atlanta, USA, aimed to find new genetic markers to identify high‑risk patients, using whole genome sequences from nearly 800 patient samples in the CoMMPass cohort.

Publishing in the journal Nature Communications, the authors explain: “The manifestation of myeloma at presentation is often confounded by a complex array of genetic alterations.

“Fortunately, modern combination therapies are mostly effective despite disease heterogeneity, with the majority of patients responding to frontline treatments that target plasma cell biology.”

However, Dr Lawrence Boise and colleagues found a DNA translocations involving the immunoglobulin lambda gene, particularly with the oncogene MYC, in about 10% of patients – which was linked to significantly worse progression-free and overall survival.

The marker is a type of chromosome rearrangement that may indicate resistance to immunomodulatory drugs such as lenalidomide, which are now standard therapies for the disease.

The team reports: “These data identify immunoglobulin lambda-MYC translocations as a marker of poor prognosis, independent of other genetic abnormalities, with implications for diagnosis and treatment.

Dr Boise says: “Most patients who have an immunoglobulin lambda 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 and dying early.

“This could be different than other markers that we currently use in myeloma, because it may influence which drugs physicians may choose in both initial treatment as well as maintenance therapy.”

Source: Barwick, B.G., Neri, P., Bahlis, N.J., Nooka, A.K., Dhodapkar, M.V., Jaye, D.L., Hofmeister, C.C., Kaufman, J.L., Gupta, V.A., Auclair, D., Keats, J.J., Lonial, S., Vertino, P.M., Boise, L.H. (2019) “Multiple myeloma immunoglobulin lambda translocations portend poor prognosis”, Nature Communications, available from doi: 10.1038/s41467-019-09555-6


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