Advancements in Acute Myeloid Leukemia Detection

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A New Assay Enhances AML Detection and Treatment
Researchers have developed a new assay for detecting a critical molecular marker in acute myeloid leukemia (AML), as detailed in a recent study published in The Journal of Molecular Diagnostics. This assay focuses on identifying the KMT2A gene fusions in AML, a development that could significantly influence treatment strategies and patient monitoring.

The Importance of Detecting Measurable Residual Disease
AML, an aggressive form of blood cancer, affects approximately 120,000 individuals globally each year. Detecting measurable residual disease (MRD) during treatment is crucial for guiding prognosis and treatment decisions. Current methods, including bone marrow morphology, multiparameter flow cytometry (MPFC), and DNA sequencing, have limitations in sensitivity, cost, or standardization.

The Novel Assay and Its Methodology
The new assay, developed by a team led by Dr. Grant A. Challen of the Division of Oncology at Washington University School of Medicine in St. Louis, employs droplet digital PCR for sensitive detection of KMT2A gene fusions. This technique is adept at identifying the five most common KMT2A fusion partners –AF9, AF6, AF4, ELL, and ENL—which account for about 80% of all KMT2A fusions. The assay works by partitioning cDNA molecules into microfluidic droplets, followed by a targeted assay with specific primers and probes.

Benchmarks and Results
The team validated their assay using human cell lines and patient samples, demonstrating its effectiveness in identifying KMT2A fusions. Notably, the assay does not produce false positives in samples from healthy individuals and can be adapted to detect additional oncogenic fusions.

Potential Impact on Treatment and Monitoring
Dr. Challen highlighted the potential of this assay in treatment decision-making and therapy response assessment by explaining that accurate detection of treatment effectiveness is critical for determining whether to escalate therapy or consider a hematopoietic stem cell transplant.

“This is a robust new tool for sensitive KMT2A fusion detection that is directly applicable for disease detection in patients with leukemia driven by these fusions,” stated Challen. “It fills a void for oncogenic fusion detection and provides some technical improvements. The assay is also scalable—additional fusions can be easily added to the assay—to expand coverage for other oncogenic fusions. We are improving blood cancer detection one drop at a time!”