Pediatric acute myeloid leukemia (AML) accounts for about 25% of childhood cancer cases. While survival rates have risen dramatically in the past few decades, 30% of patients still experience relapse. Fortunately, recent studies have uncovered a variety of genetic abnormalities specific to the disease that both (A) provide important hints about its pathogenic/clinical course and (B) may serve as therapeutic targets for future treatment.

A recent publication dug deeper into one of these abnormalities, the RUNX1/USP42 gene fusion, in a small cohort of pediatric AML patients. RUNX1 is a known disease driver across all AML ages and subtypes. It’s been found fused to more than 50 different genes, some of its better known partners being RUNX1T1, ETV6, and MECOM. These fusions are associated with varying prognoses, depending on disease subtype, age, and accompanying abnormalities. Many RUNX1 fusions, however, are still poorly understood, and infrequent enough that their prognostic implications remain hazy – including RUNX1/USP42. This team investigated the fusion in an effort to better characterize its role in AML progression.

The cohort consisted of 3 pediatric AML patients found to have RUNX1/USP42 fusion. (At the time of the study, only 12 cases of the fusion had been reported, making this the largest cohort study to date.) For all 3 patients, conventional karyotype analysis revealed a reciprocal translocation between chromosome 7 and 21. This ruled out the possibility of many of the more frequent RUNX1 fusions, and lead the team to test for RUNX1/USP42. FISH analysis verified the presence of the fusion in each patient. All 3 also harbored additional abnormalities, the most common being 5q and 11p deletions. Aberrant CD56 and CD57 cell expressions were also frequent.

Small studies like this are easy to gloss over, but their utility shouldn’t be underestimated. This team was able to expand on an incredibly rare AML-specific gene fusion, one that could’ve been easily ignored if it wasn’t for careful genetic testing. Then, drawing on the 12 cases of RUNX1/USP42-positive AML already reported, they managed to narrow in on several unique genetic and clinical features shared by these patients. Findings like these are invaluable in cancer detection, monitoring, and profiling, especially for subtypes, like pediatric AML, with a high rate of relapse.