Clinicopathologic and Molecular Characterization of NUP98-Rearranged Acute Leukemias

Introduction: NUP98 rearrangements are rare in acute leukemias and portend a poor prognosis. Methods: This study explored clinicopathologic and molecular features of five patients with NUP98 rearranged (NUP98-r) acute leukemias, including three females and two males with a median age of 34 years. Results: NUP98 fusion partners were associated with distinctive leukemia characteristics and biology. Three patients had NUP98::NSD1-r acute myeloid leukemia (AML, all cytogenetically cryptic and with concomitant FLT3-ITD) and unfavorable prognoses (in two patients), one patient had NUP98::HOXA9-r AML with morphologic and immunophenotypic features resembling acute promyelocytic leukemia, and lastly, one patient had previously underreported NUP98::MLLT1-r B/T mixed phenotype acute leukemia. After a median follow-up of 24.7 months, median overall survival was 30 months and three of five patients (60%) remained in complete remission at the last follow-up. Conclusion: Our study expands the clinical and molecular spectrum of NUP98-r acute leukemias and recommends FISH testing for NUP98 rearrangement on those leukemia cases without recurrent gene rearrangements and/or normal karyotype followed by molecular confirmation to improve timely diagnosis and clinical management.