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Effect of UTX Loss in Multiple Myeloma

By: Joseph Cupolo
Posted: Thursday, November 9, 2017

According to the findings of a recently published study in the journal Cell Reports, loss or inactivation of the histone demethylase UTX alters the transcriptional profile of multiple myeloma cells. UTX-mutant cells have shown increased sensitivity to inhibition of the histone methyltransferase EZH2. For clinicians, the altered transcriptional poise of UTX-deficient cells may offer a therapeutic opportunity, such as the continued development of EZH2 inhibitors, for patients with multiple myeloma.

“The loss of UTX leads to deactivation of gene expression, ultimately promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of multiple myeloma cells,” wrote Jonathan D. Licht, MD, Director of the University of Florida Health Cancer Center, Gainesville, and colleagues. “However, rebalancing UTX/PRC2 activity with the use of EZH2i reactivates tumor suppressor programs and alters differentiation states, ultimately leading to multiple myeloma cell death.”

UTX mutations/deletions are found in 3% to 4% of primary multiple myeloma specimens and are common features of multiple myeloma cell lines, with 30% to 40% of them presenting damaging lesions of this gene. In the study, most of the multiple myeloma cell lines were established from extramedullary multiple myeloma and plasma cell leukemia cases, suggesting UTX loss may contribute to disease progression.