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Leukemia patients may benefit from existing cancer medication
Researchers at the Knight Cancer Institute at Oregon Health & Science University have made a new discovery giving hope to patients suffering from two types of leukemia previously thought untreatable. They have hypothesized about a new and efficient way to diagnose these types of leukemia. The discovery also leads to believe that existing treatment for different types of cancer may be used to treat this two forms of leukemia.

The study isolated the molecular mutation that causes chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) in some patients. That specific mutation, found to occur in a gene called colony stimulating factor 3 receptor (CSF3R), begins a chain reaction involving other cancer-related gene families known as SRC, JAK, and TNK2, which in turn activates and drives these diseases.

This discovery is useful in that it will greatly aid physicians by providing an effective diagnosing method for these types of leukemia, which currently present difficulties for physicians to distinguish from other types of leukemia. Moreover, the study results suggest that these patients, previously thought to be beyond help, could be helped by existing FDA-approved drugs, targeting other types of cancer, which were designed to inhibit the chain reactions impacting JAK and SRC/TNK2. Clinical trials are needed to prove this concept, though.

"Our ability to rapidly pinpoint a new cancer-driving mutation demonstrates the power of integrating improved genome sequencing technology. It will accelerate our ability to tailor treatments to individuals and each research victory gives us more insight into the nature of this complex disease. What distinguished this research was our method for matching voluminous amounts of gene sequencing data with drug sensitivity data to quickly deduce which mutations were relevant in causing disease. This allows us to make a difference for patients who don't currently have good therapeutic options." - said Jeffrey W. Tyner, Ph.D., an assistant professor with the OHSU Knight Cancer Institute and Cell & Developmental Biology Department, chef of the study leading laboratory.

Tyner and the other researchers on this study used a combination of tests that are not yet commonly deployed for testing primary cancer specimen, and noted it showed success. They first performed gene sequencing on specimens from 27 patients, creating an experimental profile of the possible genetic causes of these diseases. This subsequently enabled them to highlight the important mutations that were found to be common among CNL and aCML patients. Simultaneously to gathering information about the possible genetic markers, they performed tests on fresh cell samples from these patients, testing the effects of different drugs. This enabled the teams to link, with substantial statistical significance, drug efficacy to CSF3R gene mutations.

This approach from two sides simultaneously allowed the researchers to identify a primary cause of these rare forms of leukemia. Of the 27 patients in the study, 16, or about 59 percent, had the CSF3R mutation.
"This approach allows us to rapidly discover mutations that are fundamental to cancer growth and identify drugs that might be used to combat them. Our findings are not only promising for the treatment of patients with CNL and aCML but also validate our approach to identify new drug targets in cancer." said Julia Maxson, Ph.D., of the OHSU Knight Cancer Institute, who was first author on the study.

During the study period, a CNL patient was given the FDA-approved drug ruxolitinib, which is designed to inhibit the cancer cell growth initiated by the CSF3R mutation. This novel treatment resulted in a dramatic improvement in the patient's condition.

CNL and aCML impact up to several hundred patients in the United States each year. Patients suffering from these conditions typically live only two to three years post diagnose. These forms of cancer have also been difficult to even diagnose because there wasn't enough known about their primary genetic drivers. Knowing that they are defined by mutations in CSF3R provides physicians with a means to confirm a diagnosis. Tests for this mutation have already been available, yet no one knew that they can be used to diagnose this specific conditions; the OHSU Knight Diagnostic Laboratories' GeneTrails panel for leukemia has the capability to check for this mutation.

Jerald Radich, M.D., of the Fred Hutchinson Cancer Research Center in Seattle, wrote that the approach is "an example of what genetically informed treatment may look like in the near future. This is how we will beat cancer, one gene, one disease at a time."

The study was published in the May 9 edition of the New England Journal of Medicine
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