USC Studies Chronic Myeloid Leukemia

By Leslie Ridgeway on September 10, 2009 7:36 AM

Researchers at the Keck School of Medicine of USC and the National Institute of Arthritis and Musculoskeletal and Skin Diseases have discovered high concentrations of a specific mutator protein in cells that develop resistance to drug treatment in chronic myeloid leukemia.

The finding helps explain why chronic myeloid leukemia cells become drug-resistant and may lead to the development of therapies that improve survival in patients.

Researchers led by Markus Müschen, director of the leukemia and lymphoma program at the USC Norris Comprehensive Cancer Center, found that the protein, activation-induced cytidine deaminase, which normally mutates antibody genes in B cells, triggers resistance to Gleevec, the standard treatment for chronic myeloid leukemia patients.

Chronic myeloid leukemia cells often develop resistance to Gleevec, limiting treatment options for many patients living with the illness.

The multi-investigator study, which features major contributions from USC faculty colleagues Michael Lieber, John Groffen, Yong-mi Kim and Nora Heisterkamp, is published in the current issue of Cancer Cell.

“Before this, we did not know why some patients developed resistance to Gleevec,” Müschen said. “Now that we know at least one mechanism, we can work to develop therapies to counter the effects of activation-induced cytidine deaminase in the chronic phase of the disease.”

Every year, 4,500 patients are diagnosed with chronic myeloid leukemia in the United States; nearly 25,000 have the disease today. Chronic myeloid leukemia is a slowly progressing cancer that usually occurs during or after middle age and rarely occurs in children. Patients with the disease have an unusually high number of hematopoietic stem cells (blood cell progenitors) that were slated to become immune system cells that instead develop into cancerous cells that damage the bone marrow and blood.

Gleevec increases overall survival for chronic myeloid leukemia patients to 95 percent over a five-year period. When patients develop resistance to the drug, they quickly transition from the chronic phase of chronic myeloid leukemia to a condition called blast crisis progression, or fatal B lymphoid blast crisis, with an average survival range of less than seven months.

The ongoing project is supported by two research grants from the National Institutes of Health.

TAGS: medicine

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