Myeloid sarcoma with NPM1 mutation may be clinically and genetically distinct from AML with NPM1 mutation: a study from the Bone Marrow Pathology Group

Leuk Lymphoma. 2023 May;64(5):972-980. doi: 10.1080/10428194.2023.2185091. Epub 2023 Mar 24.


Myeloid sarcoma (MS) is currently considered equivalent to de novo acute myeloid leukemia (AML); however, the relationship between these entities is poorly understood. This retrospective multi-institutional cohort study compared 43 MS with NPM1 mutation to 106 AML with NPM1 mutation. Compared to AML, MS had more frequent cytogenetic abnormalities including complex karyotype (p = .009 and p = .007, respectively) and was enriched in mutations of genes involved in histone modification, including ASXL1 (p = .007 and p = .008, respectively). AML harbored a higher average number of gene mutations (p = .002) including more frequent PTPN11 mutations (p < .001) and mutations of DNA-methylating genes including DNMT3A and IDH1 (both p < .001). MS had significantly shorter overall survival (OS) than AML (median OS: 44.9 vs. 93.2 months, respectively, p = .037). MS with NPM1 mutation has a unique genetic landscape, and poorer OS, compared to AML with NPM1 mutation.

Keywords: Hematopoiesis; genetic and other predisposing conditions; leukemic progenitor cells; myeloid leukemias and dysplasias; neoplasia.

Plain language summary

First study comparing genetic profiles of MS and AML with a common disease-defining lesion.NPM1Mut MS may be genetically distinct from NPM1Mut AML.NPM1Mut MS may have inferior overall survival compared to NPM1Mut AML.

MeSH terms

  • Bone Marrow / pathology
  • Cohort Studies
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Prognosis
  • Retrospective Studies
  • Sarcoma, Myeloid* / diagnosis
  • Sarcoma, Myeloid* / genetics
  • Sarcoma, Myeloid* / pathology


  • Nuclear Proteins
  • Nucleophosmin