Waking Silenced Genes Slows Progress of Multiple Myeloma

Cancer researchers have found that by "waking” a group of silenced genes they could induce multiple myeloma (MM) cells to enter an apoptotic pathway leading to cell death.

Investigators at Uppsala University (Sweden) used an integrative genomics approach to define the nature of the underexpressed gene expression profile in MM when compared to normal plasma cells.

They reported in the July 9, 2010, online edition of the journal PLoS ONE that the silenced genes had a common denominator in being targets and controlled by the Polycomb repressor complex (PcG).

Polycomb-group proteins are a family of proteins first discovered in fruit flies that can remodel chromatin so that epigenetic silencing of genes takes place. In humans, Polycomb Group gene expression is important in many aspects of development. Mouse mutants lacking PRC2 genes die as embryos while most PRC1 mutants are born alive but with anatomic rearrangements that cause them to die shortly after birth. In contrast, overexpression of PcG proteins correlates with the severity and invasiveness of several cancer types.

In this study, the investigators treated MM cells with chemical compounds able to "awaken” the expression of the silence PcG genes. They reported that activation of the genes resulted in reduced proliferation and increased apoptosis in human MM cell lines.

"A new strategy for treating multiple myeloma could be to develop drugs that are targeted to the PcG complex, leading to reactivation of the silenced gene profile,” said senior author Dr. Helena Jernberg Wiklund, professor of genetics and pathology at Uppsala University. "This silencing may lead to the uncontrolled growth of the malignant cells.”

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