Scientists identify all genes that could predict clinical outcomes in patients with FLT3-ITD AML -
Novel discovery by scientists NUS improves the profile of patients LAM for targeted therapies
Test Dnmt3a mutations in FLT3-ITD subgroup of AML patient at the point of diagnosis and post-chemotherapy could improve treatment and to predict the risk of relapse and rates survival respectively
researchers from the Singapore cancer science Institute (CSI Singapore) at the national University of Singapore (NUS) have identified a set of genes, including Dnmt3a which could potentially be used to predict clinical outcome of patients with a type of acute myeloid leukemia (AML) associated with a FLT3 internal tandem duplication (FLT3-ITD) mutation.
specifically, the research team led by Professor Phillip H. Koeffler, senior principal researcher at CSI Singapore, found that chemotherapy can cause genes to mutate further in patients with ITD FLT3- AML. The researchers also identified Dnmt3a as a potential marker for monitoring response to chemotherapy patient because patients with this mutation in remission courses tend to have little disease free and low overall survival.
The results, which were published online in the blood, a medical journal published by the American Society of Hematology, contribute to the understanding of the molecular underlying causes of FLT3-ITD AML and present opportunities for scientists to develop effective targeted therapies.
poor clinical outcomes associated with FLT3-ITD AML
AML is a cancer of the blood characterized by the rapid growth of abnormal white blood cells, and its incidence increases with age. AML occurs as a result of inherited genetic mutations or acquired. About 20 to 30 percent of AML patients have a specific genetic mutation called FLT3-ITD, which promotes the aberrant growth of cancer cells. The prognosis for this subgroup of patients is often associated with poor clinical outcomes and higher relapse rates.
Although 70 percent of FLT3-ITD AML patients achieve complete remission with conventional chemotherapy, the majority of these patients eventually relapse and die of leukemia resistant to therapy. Therefore, there is an urgent need to identify genomic abnormalities underlying this subtype AML both at diagnosis and relapse to help scientists better understand this disease.
The research team at CSI Singapore, tested 80 samples of patients to discover the mutational spectrum associated with disease relapse. The research team mutations on genes that are essential for cell maintenance and identified a set of genes, particularly Dnmt3a be recurrent mutated.
Dnmt3a as a genetic marker for more effective detection of AML patients for targeted therapy
"The results of this study suggest that chemotherapy may induce new genetic mutations in patients with FLT3-ITD AML, which eventually causes the majority of these patients eventually suffer relapse and develop a resistant leukemia treatment with low survival rate. more specifically, we found that Dnmt3a mutations are the most stable mutations . therefore, patients who have undergone chemotherapy can test for the presence of mutations Dnmt3a by analyzing blood samples to determine if cancer cells are always present and the likelihood of relapse. It may also serve as a marker the point of diagnosis for the selection of appropriate treatment, "said Professor Koeffler.
In addition, the study also identified a number of new genes that contribute to leukemia and the results can be the basis for further investigation potential avenues of treatment for AML. Prof Koeffler and his team are now delving deeper into the potential role and mechanisms of the genes identified in the development of leukemia.
EmoticonEmoticon