Genetic Testing in AML: Dr. Ghayas Issa Highlights Key Strategies

Dr. Ghayas C. Issa, a prominent clinical and translational researcher at The University of Texas MD Anderson Cancer Center, has outlined essential strategies for genetic testing in acute myeloid leukemia (AML). His focus on alterations in NPM1 and KMT2A underscores their significance in informing prognosis and guiding treatment decisions.

Issa highlighted that testing for NPM1 mutations has been recommended as a standard practice. This testing is crucial even prior to the advent of menin inhibitors, as it provides vital prognostic insights. According to Issa, identifying NPM1 mutations can significantly influence treatment pathways, including the determination of transplant eligibility. The most effective method for detecting this mutation is through next-generation sequencing (NGS).

At the time of relapse, retesting for NPM1 mutations becomes particularly important, as about 5% of cases may lose the NPM1 mutation. Issa explained that this loss can indicate the presence of other mutations that may be driving the leukemia’s progression.

Importance of KMT2A Testing

With the emergence of menin inhibitors, the relevance of testing for KMT2A alterations has grown. Issa stated that understanding a patient’s KMT2A status is now crucial for determining their eligibility for these innovative treatments. The most commonly used test for identifying KMT2A rearrangements is fluorescence in situ hybridization (FISH).

Issa noted that, unlike NPM1 mutations, KMT2A alterations are typically founding events in the disease’s development, indicating that they are likely to remain present at relapse. However, he cautioned that there is a possibility of missing a KMT2A rearrangement at diagnosis, especially if it is not immediately evident in the initial cytogenetic analysis. Therefore, repeating FISH at the time of relapse is essential, particularly if thorough testing was not conducted during diagnosis.

Through his insights, Dr. Ghayas Issa emphasizes the critical role of genetic testing in AML, paving the way for tailored treatment approaches and improving patient outcomes. As research progresses, these strategies will play a vital role in enhancing the management of this challenging disease.