A Step Toward Personalized Care of Leukemia Patients

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Researchers have discovered gene mutations in patients with acute myeloid leukemia (AML) that may help doctors determine which treatments will work best for which patients early on. Patients with AML, a cancer of the blood, have a 20% five-year survival rate overall, but the new discoveries may increase the chances of survival for certain patients.

After diagnosis, AML patients are categorized as having one of three outcome risk profiles. Those with a favorable prognosis are treated with standard chemo and radiation therapy. Patients with poor outcome risk are treated aggressively earlier, with a bone-marrow transplant after high-dose chemotherapy. Then there are the more than half of all AML patients who have an intermediate-risk profile; these patients are also treated with standard therapy, but for unknown reasons some respond well and some do not. Patients whose cancer returns after initial treatment must then undergo more aggressive therapy with a bone marrow transplant. (More on Time.com: Radiation May Be a Greater Cancer Risk for Adults Than Doctors Thought).

What doctors have sought is a way to predict before treatment begins which intermediate-risk patients would do better with bone marrow transplant at the outset.

Researchers from the Genome Center at Washington University School of Medicine in St. Louis have taken a significant step toward answering that question. By decoding the genome of a leukemia patient, the scientists isolated a mutation in one gene — DNA methyltransferase 3A gene (DNMT3A), which controls DNA methylation or how a gene is expressed. They sequennced DNMT3A in 281 cancer patients and found the mutation in 22.1% of patients. The mutations were associated with low survival: patients with the DNMT3A mutations survived about a year after diagnosis, compared with nearly three-and-a-half years for patients without the mutations. (More on Time.com: An Insurer Aims to Put Your Oncologist on a Budget).

Interestingly, the mutations were found in 33.7% of patients with intermediate outcome risk, and in none of the patients with favorable risk. (Few people with poor outcome risk had the mutation: only 6 of 36 patients.) Among patients with the mutations, those who were treated with bone marrow transplants did better than those who were treated with standard chemotherapy.

According to the study’s lead author, oncologist and geneticist Dr. Timothy Ley, the types of mutations identified are particularly unusual, with characteristics of two common types of mutation that have not been seen in combination before.

“This gene has the signature of a tumor suppressor in that the mutations are all over the gene and kill the gene — known as a loss-of-function mutation,” says Ley. The BRCA-1 mutation, which is associated with an increased rate of breast cancer, is another example of a loss-of-function mutation. (More on Time.com: Pregnant Women with Breast Cancer Should Do Chemo).

However, Ley continues: “The odd thing about this gene is that more than half the mutations in the gene are in one amino acid, which usually suggests that that mutation is doing something novel. A gain-of-function mutation causes the cell to do something new, and the genetic footprint [of the DNMT3A mutation] suggests that it might be doing something new.” (More on Time.com: The Landscape of Cancer Treatment).

If further data supports the findings of the Washington University scientists, it could lead to the development of a diagnostic test that could quickly identify AML patients with the mutations. It may also help open a new line of drug development that targets the relevant mutations.

Better targeted cancer treatment based on personalized medical profiles is a major priority in the medical community. Recently, Dr. Francis Collins, director of the National Institutes of Health, identified genetic diagnostics as a key area through which the health-care system could streamline treatment, reduce costs and improve patient outcomes.

The new study was published in the Nov. 11 edition of the New England Journal of Medicine.

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