A novel assay that detects a unique molecular marker in patients with acute myeloid leukemia (AML) may revolutionize the way this disease is detected and treated according to a new report in The Journal of Molecular Diagnostics published by Elsevier. This assay may improve detection of AML driven by KMT2A gene fusions and may affect treatment decision-making, assessing response to therapy, and long-term surveillance.

AML is a rare, aggressive blood cancer diagnosed in around 120,000 individuals worldwide each year. Detecting residual disease during treatment is essential for determining prognosis and guiding treatment decisions. Currently, the methods for detecting measurable residual disease (MRD) during treatment for AML include bone marrow morphology, multiparameter flow cytometry (MPFC), and DNA sequencing. Morphologic assessment only detects leukemic cells at a 5% limit of detection. MPFC has a more sensitive limit of detection at 0.01% to 0.001%, but is challenging to implement and interpret, and is not standardized between laboratories. DNA sequencing approaches can identify leukemic cells by their somatic mutation profile but are expensive and can be confounded by clonal hematopoiesis in non-leukemic blood cells.

Lead investigator Grant A. Challen (and Gabrielle’s Angel Foundation grantee), PhD, Division of Oncology, Department of Medicine, Washington University School of Medicine in St. Louis, explains, “Oncogenic fusions are often disease-defining and present a unique marker of leukemic cells that are not usually present in healthy cells. Other diseases such as chronic myeloid leukemia (CML) can already be tracked by the canonical BCR-ABL fusion and sensitively detecting these fusions has revolutionized how CML is treated. For AML patients with oncogenic fusions driving their disease, the KMT2A fusion is a molecular marker that can be leveraged for sensitive MRD detection. We therefore wanted to develop a platform for sensitive KMT2A fusion-detection to improve how we detect and treat this disease.”