UCSD researchers study leukemia markers to find vulnerabilities in the cancer

SAN DIEGO (KUSI) – A team of researchers at the UC San Diego School of Medicine and Moores Cancer Center used genome technology to identify key markers of an aggressive type of leukemia, which may help pinpoint the cancer’s weaknesses, the university reported Monday.

The researchers used CRISPR technology — a technology which identifies families of DNA sequences — to identify key regulators of aggressive chronic myeloid leukemia, a type of cancer that remains difficult to treat and is marked by frequent relapse.

“We used CRISPR technology to carry out a genome-wide screen in leukemia cells to block thousands of genes at once. This is an extremely powerful tool that allowed us to identify a multitude of genes that fuel leukemia growth and find new vulnerabilities that can be targeted in this disease,” said senior author Tannishtha Reya, a professor in the departments of pharmacology and medicine.

“The study also shows, for the first time, that whole genome CRISPR- based screens can in fact be carried out in a manner that is much more physiologically relevant: using primary cancer cells, and in the setting of the native microenvironment,” she said.

In the study — published in the April 20 online edition of the journal Nature Cancer — Reya and her colleagues identified RNA-binding proteins — which normally control how, when and if cells make certain proteins — as a key class of proteins that sustain and protect drug-resistant leukemia stem cells.

The authors focused on Staufen2, a relatively understudied member of the RNA-binding protein family that was previously only known to control brain and nervous system development.

“We are particularly excited about this work because, to our knowledge, this is the first demonstration that Staufen2 is a key dependency in any cancer,” Reya said.

According to the National Cancer Institute, about 1.5 percent of men and women will be diagnosed with leukemia at some point during their lifetimes. While chronic myeloid leukemia can be controlled with targeted therapies, the disease can be lethal if it advances or is diagnosed in an acute “blast” phase. The findings also have implications for acute myeloid leukemia and other blood cancers.

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