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Gene Expression and Progression of Multiple Myeloma

By: Cordi Craig
Posted: Thursday, February 21, 2019

Researchers may have identified molecular signatures that indicate the progression of multiple myeloma, according to a gene-sequencing study published in the Blood Cancer Journal. Jin Sung Jang, PhD, of the Mayo Clinic, Rochester, Minnesota, and colleagues suggested that the new signature may help predict patient prognosis and treatment stratification, although the findings require validation in a larger patient cohort.

Using single-cell RNA sequencing, the authors examined molecular heterogeneity in CD138-positive cells (n = 597) from bone marrow aspirates of 15 patients with multiple myeloma at different stages of disease progression. The investigators selected 790 genes and organized cells into 4 main groups (L1 to L4) using unsupervised clustering.

The four clustering groups corresponded with increasing risk levels of multiple myeloma. Patients in the L1 group, the minimal risk cluster, contained plasma cells derived from monoclonal gammopathy of undetermined significance, the condition preceding multiple myeloma. Compared with the L1 cluster, patients in the later groups (L2, L3, and L4) with a higher number of genes involved in protein homeostasis in multiple myeloma cells were associated with disease progression and lower rates of survival. There was a strong association between a 44-gene signature with consistently overexpressed genes and poorer overall survival (P < .0001). The relationship was particularly strong among those treated with bortezomib (P < .0001).

“It will also be highly informative to determine whether the fraction of plasma cells within different risk clusters change over time in individual patients [with multiple myeloma] and how they affect disease progression, treatment response, and patient outcome,” the authors concluded.

Disclosure: The study authors reported no conflicts of interest.



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