New insights into the clinical characteristics of SETD2‐mutated acute myeloid leukaemia

Abstract

SETD2 is the only H3K36me3 methyltransferase, and it has been reported to act as a tumour suppressor in a variety of cancers. Our previous study showed that Setd2 deficiency in the haematopoietic system led to the malignant transformation, which provided evidence of its tumour suppressor role in haematopoiesis. 1,2 Consistently, SETD2 mutation has been found to affect 12% of acute lymphoblastic leukaemia (ALL) and 8% of acute myeloid leukaemia (AML). 3,4 In ALL, the distribution pattern of SETD2 mutation has been well established. Previous findings have indicated that SETD2 mutation tends to co-occur with KMT2A rearrangements, ETV6::RUNX1 and TCF3::PBX1. [3][4][5] By contrast, the knowledge of SETD2 mutation in AML is still poorly understood. Recently, some sporadic studies have shown that SETD2 mutation is recurrent in KMT2A-rearranged and CBFrearranged AML. 4 Our results showed SETD2 mutation to occur frequently in NPM1-mutated AML. 6 Due to the low incidence of AML with SETD2 mutation and lack of information regarding its clinical features, a comprehensive view of the distribution pattern and prognostic role of SETD2