Adult Acute Myeloid Leukemia with the KMT2A-Mixed Lineage Leukemia T10 Fusion: An Analysis of 10 Cases Showed Common Features and Frequent Mutations in the RAS Signaling Pathway

Mixed lineage leukemia (<i>MLL) T10</i> is a relatively rare partner for the <i>KMT2A</i> lysine (K)-specific methyltransferase 2A gene. The common features and coexisting mutations of acute myeloid leukemia (AML) patients with <i>KMT2A-MLLT10</i> remain unknown. In this study, 10 adult AML patients with <i>KMT2A-MLLT10</i> fusions were picked up from 496 AML patients by using RT-polymerase chain reaction (PCR) and/or fluorescence in situ hybridization, and then screened for mutations in the 49 genes panel with next-generation sequencing and PCR, followed by direct Sanger sequencing. Of the 10 unique individuals identified, 6 were male and 4 were female (M:F ratio, 1.5:1) with ages ranging from 19 to 52 years (median 39.5 years). Most (90%, 9/10) patients with <i>KMT2A-MLLT10</i> were accompanied by additional mutations. Twelve mutated genes were detected, averaging 2.1 mutations per patient (range, 0–4). The most frequently mutated gene was <i>NRAS</i> (<i>n</i> = 5). Clinical and laboratory data pointed to common features: French American British-M5 subtype (<i>n</i> = 7), a high rate of relapse, and biomarkers CD33 (<i>n</i> = 10), CD117 (<i>n</i> = 9), CD13 (<i>n</i> = 8), and CD64 (<i>n</i> = 8). Overall, most patients harbored at least one mutation. A high incidence of mutations affecting the RAS signaling pathway or RAS regulating components was found in 50% (5/10) patients. The overall survival is about 12.0 months. Allogeneic-hematopoietic stem cell transplantation trends to improve survival in selected patients.