Looking for tools to shut down leukemia for good

May 1, 2012 | by City of Hope Staff

Some people call it the longevity gene. It’s known as sirtuin 1, or SIRT1, and depending on who you talk to, it can either extend lifespan or limit it. And sometimes it can fight cancer, but at times it can promote the disease, too.

Photo of WenYong Chen WenYong Chen

City of Hope biologist WenYong Chen , Ph.D., is curious about its role in blood cancer. He’s targeted it as a potential survival mechanism for a form of leukemia. He and other scientists at City of Hope recently found that some chronic myelogenous leukemia cells use the gene as a life preserver, helping them stay alive during treatment.

The research is part of a scientific drive at City of Hope to end the threat of CML. Some projects look at how leukemia cells manipulate the tissue around them in the bone marrow; others focus on drugs that could potentially work together with existing treatments. Still others, like Chen’s, look at how leukemia resists today’s therapies.

Chen and his colleagues recently published a study in the journal Blood that showed that SIRT1 may be a reason that CML cells can grow resistant to the drug known as Gleevec or imatinib. Today, nine of every 10 leukemia patients taking the drug survive for at least five years, but patients can relapse.

Gleevec fights CML by blocking a mutant protein in the body that kicks off the blood cancer. By inactivating the protein, Gleevec pushes leukemia cells to wither and die — but not all of them. Why do some survive? The City of Hope team showed that leukemia cells produce a lot of SIRT1 — and SIRT1 shuts off a gene that suppresses leukemia.

Ultimately, treatment that interferes with SIRT1 could be a tool to fight this cancer in the future.

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