The prognostic significance of partner genes and breakpoint locations in children with <i>KMT2A</i>-rearranged acute myeloid leukemia

Acute myeloid leukemia (AML) with KMT2A rearrangements is one of the most common AML subtypes in children. KMT2A rearrangements are extremely heterogeneous because of different breakpoint locations in the DNA of this gene in combination with a large number of various partner genes. Patients with KMT2A-rearranged AML are typically stratified into a high-risk group. However, there are reports of different prognostic significance of different rearrangements of this gene found both in Russian and international literature. For example, several studies including both adults and children suggested that AML with t(1;11)(q21;q23.3)/KMT2A::MLLT1 and t(9;11)(q21;q23.3)/KMT2A::MLLT3 translocations had a more favorable prognosis. However, these findings failed to be reproduced in other studies. What is more, a number of studies stated that the prognosis of survival in patients aged 0–24 months affected by KMT2A-rearranged acute leukemia may depend not only on the partner gene but also on the location of a breakpoint in the KMT2A gene, while also saying that patients with a breakpoint in intron 11 have the worst prognosis. Here, we aimed to evaluate the prognostic significance of KMT2A rearrangements in children with AML. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of Russia. We concluded that specific partner gene and breakpoint location did not have any significant influence on treatment outcomes in children with KMT2A-rearranged AML who had been treated according to the AML-MRD-2018 protocol. These findings may indicate that such patients should be stratified into a high-risk group irrespective of the involved partner gene and breakpoint location.