Clinical implications of NUP98::NSD1 fusion at diagnosis in adult FLT3‐ITD positive AML

Abstract Objectives The cryptic fusion oncogene NUP98::NSD1 is known to be associated with FLT3 ‐ITD mutation in acute myeloid leukemia (AML), and an independent poor prognostic factor in pediatric AML. However, there are little data regarding the clinical significance of NUP98::NSD1 in adult cohort. Methods We conducted a multicenter retrospective study to investigate the prevalence, clinical characteristics, and prognostic impact of NUP98::NSD1 in adult FLT3 ‐ITD‐positive AML patients. Results In a total of 97 FLT3 ‐ITD‐positive AML patients, six cases (6.2%) were found to harbor the NUP98::NSD1 fusion transcript. NUP98::NSD1 positive cases had significantly higher platelet counts and a higher frequency of FAB‐M4 morphology than NUP98::NSD1 negative cases. NUP98::NSD1 was found to be mutually exclusive with NPM1 mutation, and was accompanied by the WT1 mutation in three of the six cases. The presence of NUP98::NSD1 fusion at the time of diagnosis predicted poor response to cytarabine‐anthracycline‐based intensive induction chemotherapy (induction failure rate: 83% vs. 36%, p = .038). Five of the six cases with NUP98::NSD1 underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two of the five cases have successfully maintained remission, with one of them being rescued through a second HSCT. Conclusions Detecting NUP98::NSD1 in adult FLT3 ‐ITD‐positive AML is crucial to recognizing chemotherapy‐resistant group.