Genetic Mutation Can Predict Acute Myeloid Leukemia Risk a Decade Before Diagnosis

While there are known risk factors of developing acute myeloid leukemia (AML) — such as a myelodysplastic syndrome diagnosis and receiving chemotherapy and radiotherapy – a diagnosis can still stun an individual. But researchers at Weill Cornell Medicine and New York-Presbyterian recently discovered a genomic pre-malignant biomarker of the disease that can identify people who are at a greater risk for AML.

In their findings, which were recently published in the journal Nature Medicine, the researchers identified eight high-risk genes that, if mutated, can be associated with a 30- to 50-fold increase in developing the disease.

“Our study showed that mutations that increase risk of AML can be present over a decade before diagnosis, thus providing a window of opportunity,” study author Pinkal Desai, M.D., hematologist-oncologist at Weill Cornell Medicine and New York-Presbyterian, said in an interview with CURE.

The researchers used the Women’s Health Initiative to examine blood samples from 200 women who went on to develop AML and compared the samples to 200 healthy women. They found that 69 percent of the women in the AML group had mutations in one of the following genes: IDH1/2, TP53, DNMT3A, TET2, SRSF2, SF3B1 and U2AF1. Less than one-third (31 percent) of the women in the control group had a mutation of one of these genes.

The implications of these findings could be two-fold. First, they might set the stage for more research on at-risk patients, and it can also lead to the development of drugs that can better treat — or even prevent – AML.

“People with these mutations can be monitored closely for AML risk and, with future research, intervention approaches can be envisioned to prevent the onset of AML,” Desai said.

This is particularly important since currently, the prognosis of patients who are over the age of 65 and diagnosed with AML is poor. Not to mention, treatment for the disease — which often involves stem cell transplant – comes with complications and potential morbidity on its own. Preventing the disease altogether would be “instrumental” in reducing mortality, according to Desai.

The findings also provide reason for all patients who are diagnosed with AML to undergo genetic testing.

“Patients with AML should absolutely undergo mutational testing as part of the work-up of the disease,” Desai said. “Our study is a step ahead of that in the concept that the mutations that may occur as part of AML can be detected before the disease develops, thus identifying individuals at high risk.”

Moving forward, the research team hopes to conduct larger studies to find potentially life-saving interventions. These can include treatments that specifically target the mutation that is contributing to the disease, or novel approaches that stop disease progression before it turns into AML, said Desai.

“Our ultimate goal is to conduct long-term prospective studies to further investigate the utility of monitoring and intervention in helping patients,” added study author Duane Hassane, Ph.D., leukemia genomicist at Weill Cornell Medicine.