Multiple myeloma is one of the most common blood cancers, and at present considered to be incurable. In a new study from Uppsala University, researchers now present a conceptually new model for the development and progression of multiple myeloma. The study was done in collaboration with Vrije Universitet Brussels and is published in the July edition of the online journal PLoS ONE.
Using large cohorts of myeloma patients the researchers have identified a profile of genes that are silenced by epigenetic mechanisms in the malignant plasma cell.
"This silencing may lead to the uncontrolled growth of the malignant cells," says Helena Jernberg Wiklund, professor at the Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University and one of the investigators in the study.
The silenced gene profile was compared and contrasted to normal plasma cells, which are highly specialised and for which growth and lifetime is tightly controlled.
The silenced genes have a common denominator in being targets and controlled by the Polycomb repressor complex (PcG). This complex has previously been implicated in self-renewal and division of normal embryonic stem cells. In the study the researchers found that inhibitors of PcG also could decrease the growth of tumour cells in an animal model of myeloma.
"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," says Helena Jernberg Wiklund.
- Antonia Kalushkova., Marten Fryknas, Miguel Lemaire2 Charlotte Fristedt, Prasoon Agarwal1, Maria Eriksson, Sarah Deleu, Peter Atadja, Anders Osterborg, Kenneth Nilsson, Karin Vanderkerken, Fredrik Oberg, Helena Jernberg-Wiklund (2010). Polycomb Target Genes Are Silenced in Multiple Myeloma. PLoS ONE, 5(7): e11483 DOI: 10.1371/journal.pone.0011483
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