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.
Keywords: FLT3-ITD; Gilteritinib; Hokkaido leukemia net (HLN); NUP98::NSD1; North Japan Hematology Study Group (NJHSG); induction failure.
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