A novel fusion gene of NUP98::CYP2F2P in myeloid neoplasm

We report the first identification of an NUP98::CYP2F2P gene fusion in a 60-year-old woman presenting with pancytopenia and 6.5% bone marrow blasts. CYP2F2P, a cytochrome P450 pseudogene, represents the first reported pseudogene partner in the CYP family for NUP98 rearrangements. Comprehensive molecular characterization revealed this novel fusion transcript alongside a complex karyotype. While conventional diagnostic criteria (including the 2022 ICC guideline) would have classified it as myelodysplastic syndrome (MDS), the patient exhibited primary resistance to four cycles of azacitidine, with persistent 6.5% blasts and minimal residual disease at 7.16%. The case was reclassified as AML based on 2022 WHO 5th classification recognizing NUP98 rearrangements as disease-defining regardless of blast percentage. These findings regarding the diagnostic blast threshold for NUP98-rearranged myeloid neoplasms and highlights the need for further investigation with larger cohorts to better define these boundaries. In conclusion, this case reported a novel fusion gene of NUP98::CYP2F2P in myeloid neoplasm and suggested that the blast threshold for AML with NUP98 rearrangements should be further investigated to guide treatment standardization.