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

Abstract

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.

Key Points

• First study comparing genetic profiles of MS and AML with a common disease-defining lesion.

• NPM1^Mut MS may be genetically distinct from NPM1^Mut AML.

• NPM1^Mut MS may have inferior overall survival compared to NPM1^Mut AML.

Keywords:

• Hematopoiesis
• leukemic progenitor cells
• neoplasia
• genetic and other predisposing conditions
• neoplasia
• myeloid leukemias and dysplasias

Acknowledgements

Clinical trial registration: Not applicable.

Ethical approval

This study was approved by the Institutional Review Boards of all participating institutions and patient consent was not deemed necessary.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, M.R., upon reasonable request.

Additional information

Funding

No financial support was received for this project.