Study Explores Rare Myeloid Neoplasms with NPM1 Mutations

By Keightley Amen - December 11, 2022

According to recent research, myeloid neoplasms (MNs) with NPM1 gene mutations are an aggressive subtype. The researchers, who presented their findings at the 64th American Society of Hematology Annual Meeting & Exposition, said the results support the World Health Organization’s proposal to reclassify these types of MNs into acute myeloid leukemia (AML), regardless of blast counts, so that these patients can benefit from more intensive treatments.

NPM1 gene mutations are rarely detected in patients with non-acute MNs, such as myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML),” wrote the authors, led by Chen Wang, MD, of the Department of Internal Medicine in the Morsani College of Medicine at the University of South Florida in Tampa. “Retrospective case series have suggested that they are typically associated with an aggressive disease course and progress into AML in a short period of time, representing a distinct clinicopathological entity.”

The research team sought to explore prognostic factors and long-term outcomes in this rare patient subpopulation. They collected data on 22 patients with NPM1-mutated MNs treated between 2009 and 2022 (n=16 with MDS; n=6 with CMML). Their median age at diagnosis was 66 years, and 54.5% were male. Controls were patients with AML who had a history of MDS or CMML and NPM1 mutations detected (n=31).

Most patients with MNs had a normal karyotype (72.7%), and the median variant allele frequency of NPM1 mutation was 30.7%. They had lower bone marrow blast counts than controls and tended to have fewer IDH1/2 and FLT3-ITD/TKD mutations. Most of the MN patients (77.3%) received hypomethylating agents with unsatisfactory response, and four had allogeneic hematopoietic stem cell transplantation (HSCT). Controls, on the other hand, received frontline intensive chemotherapy with a high rate of complete response (CR; 82%), with 39% progressing to allogeneic HSCT. Controls had much better overall survival (median 41 months vs 22.1 months).

Ultimately, 64% of patients with MN and NPM1 mutation transformed to AML in a median 21.1 months. Nine of them received intensive chemotherapy post-transformation, with four CRs. Other notable findings were that concurrent baseline DNMT3A mutations tended to be associated with inferior outcomes, and patients who underwent transplantation had better outcomes.


Wang C, Chan O, Al Ali N, et al. Clinical characterization and outcomes of patients with NPM1-mutated myelodysplastic syndromes or chronic myelomonocytic leukemia. Abstract #3084. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.

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