NUP98 rearranged acute myeloid leukemia: An initial experience

Background: Nucleoporin 98 ( NUP98 ) rearranged acute myeloid leukemia (AML) is a distinct category in the World Health Organization classification and is classified as an adverse risk in the 2022 European Leukemia NET Risk Stratification. These are distinct subtypes of AML, affecting both pediatric and adult AML cases, with dismal outcomes despite transplantation. Due to the rarity of occurrence, limited evidence is available, except for anecdotal cases and small series, and none yet from India. Methods: This is a single-center experience with 16 NUP98 rearranged AML from India. Clinicopathologic, immunophenotypic, and genomic details were retrieved from the medical record archives of the hospital. Results: Sixteen patients with NUP98 rearranged AML were included in the study, of which 14 were adults and two were pediatric. The median age of the adult AML patients was 27 years (range: 21–34 years). The majority of cases were M5 (7/16, 44%), followed by M1 and M4 in 4 (31%) and 5 (25%) cases, respectively. Among the 16 patients, all had nuclear receptor binding SET domain protein 1 ( NSD1) as their partner. Twelve (75%) patients harbored concurrent Fms-like tyrosine kinase 3 internal tandem duplication ( FLT 3-ITD) mutations and 56% had a pathogenic missense or truncating variant in Wilms tumor 1 ( WT1) gene. Other common concomitant genomic alterations included ten-eleven translocation 2 ( TET2) (25%), Proto-Oncogene, GTPase , ( NRAS) (19%), neurofibromin 1 ( NF1) (13%), DNA methyltransferase 3 alpha ( DNMT3A) (13%), and cohesin complex component (RAD21 ) (6%) in descending order. The median time to detection of NUP98 rearrangement was 3.3 days, and hence, induction was based on genomic findings. None of the patients achieved complete response (CR) and none underwent transplantation. Conclusion: This is a single-center experience of NUP98 rearranged AML from India, possibly the largest reported so far from the peninsula. NUP98 rearranged AML have been described to follow an aggressive and tumultuous disease course with non-achievement of CR despite intensive chemotherapy.