The landscape of NUP98 rearrangements clinical characteristics and treatment response from 1491 acute leukemia patients

Nucleoporin 98 (NUP98, chromosome 11p15) fusion oncoproteins also called NUP98 rearrangements (NUP98r) have already been identified in a spectrum of hematologic malignancies for a long time, including acute myeloid leukemia (AML), chronic myeloid leukemia in blast crisis/accelerated phase, chronic myelomonocytic leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia (ALL) especially T-ALL and mixed-phenotype acute leukemia, mostly associated with pediatric leukemias and poor prognosis [ 1 , 2 , 3 , 4 ]. NUP98r generate NUP98 fusion proteins that join the N-terminal domain of NUP98 with various C-terminal partners including HOX genes and non-HOX genes [ 1 ]. In 2022 ELN classification, NUP98r especially including NUP98::NSD1, NUP98::KDM5A and other partners were identified as AML with other rare recurring translocations [ 5 ]. In 2022 WHO classification, three AML types with characteristic rearrangements involving lysine methyltransferase 2A (KMT2A), MECOM and NUP98 were recognized [ 6 ]. It was also important to note that rearrangements involving these three genes, particularly NUP98, may be cryptic on conventional karyotyping. Although a comprehensive report about pediatric NUP98r leukemia patients has just been published recently [ 7 ], there was no overall report about adult NUP98r leukemia patients.