Genetic Marker May Improve Targeted Therapies for Acute Myeloid Leukemia
A majority of patients with specific gene mutation will eventually relapse and die of treatment-resistant leukemia.
A set of genes was recently found to be a potential marker to predict clinical outcomes of acute myeloid leukemia (AML) patients with the FLT3 internal tandem duplication (FLT3-ITD) mutation.
The gene DNMT3A may be a potential marker for monitoring patient chemotherapy response, since these patients tend to have short relapse-free survival and low overall survival rates, according to a study published in Blood. There are approximately 20 to 30% of AML patients with the FLT3-ITD mutation.
Although 70% of these patients achieve complete remission, a majority will eventually relapse and die of treatment-resistant leukemia. The researchers tested samples from 80 patients to determine the mutational spectrum associated with the relapse of the disease.
After searching for mutations on genes essential for cell maintenance, scientists identified a set of genes called DNMT3A to be recurrently mutated.
“The findings from this study suggest that chemotherapy may have induced further gene mutations in patients with FLT3-ITD AML, which eventually causes majority of these patients to eventually suffer from relapse and develop therapy-resistant leukemia with poor survival rate,” said H. Phillip Koeffler, senior principal investigator at CSI Singapore. “Specifically, we found that DNMT3A mutations are the most stable mutations. Therefore, patients who have undergone chemotherapy can test for the presence of DNMT3A mutations through the testing of blood samples to determine if the cancerous cells are still present and the likelihood of a relapse. It can also serve as a marker at the point of diagnosis for the selection of appropriate treatment.”
Researchers were also able to identify several novel genes that contribute to leukemia, and may serve as a basis for further investigation into potential treatment options for AML. Currently, the team is working on digging deeper into the potential role and mechanisms of the genes in causing leukemia.