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

Maximiliano Ramia de Cap; Leo P Wu; Christian Hirt; German A Pihan; Sanjay S Patel; Wayne Tam; Carlos E Bueso-Ramos; Rashmi Kanagal-Shamanna; Philipp W Raess; Alexa Siddon; Damodaran Narayanan; Elizabeth A Morgan; Geraldine S Pinkus; Emily F Mason; Eric D Hsi; Heesun J Rogers; Laura Toth; Kathryn Foucar; Stephanie N Hurwitz; Adam Bagg; Anton Rets; Tracy I George; Attilio Orazi; Daniel A Arber; Robert P Hasserjian; Olga K Weinberg; Bone Marrow Pathology Group

doi:10.1080/10428194.2023.2185091

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.

Authors

Maximiliano Ramia de Cap^{1

2

3}, Leo P Wu^{1

2}, Christian Hirt^{1

2}, German A Pihan^{1

2}, Sanjay S Patel⁴, Wayne Tam⁴, Carlos E Bueso-Ramos⁵, Rashmi Kanagal-Shamanna⁵, Philipp W Raess⁶, Alexa Siddon⁷, Damodaran Narayanan^{1

8}, Elizabeth A Morgan^{1

8}, Geraldine S Pinkus^{1

8}, Emily F Mason⁹, Eric D Hsi¹⁰, Heesun J Rogers¹¹, Laura Toth¹², Kathryn Foucar¹², Stephanie N Hurwitz¹³, Adam Bagg¹³, Anton Rets^{14

15}, Tracy I George^{14

15}, Attilio Orazi¹⁶, Daniel A Arber¹⁷, Robert P Hasserjian^{1

18}, Olga K Weinberg¹⁹; Bone Marrow Pathology Group

Affiliations

¹ Harvard Medical School, Boston, MA, USA.
² Beth Israel Deaconess Medical Center, Boston, MA, USA.
³ North Bristol NHS Trust, Bristol, UK.
⁴ Weill Cornell Medical College, New York, NY, USA.
⁵ The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
⁷ Yale School of Medicine, New Haven, CT, USA.
⁸ Brigham and Women's Hospital, Boston, MA, USA.
⁹ Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁰ Wake Forest Baptist Health, Winston-Salem, NC, USA.
¹¹ Cleveland Clinic, Cleveland, OH, USA.
¹² Department of Pathology, The University of New Mexico, Albuquerque, NM, USA.
¹³ Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ ARUP Laboratories, Salt Lake City, UT, USA.
¹⁵ Department of Pathology, University of Utah, Salt Lake City, UT, USA.
¹⁶ Texas Tech University Health Sciences Center, Lubbock, TX, USA.
¹⁷ Department of Pathology, University of Chicago, Chicago, IL, USA.
¹⁸ Massachusetts General Hospital, Boston, MA, USA.
¹⁹ UT Southwestern Medical Center, Dallas, TX, USA.

PMID: 36960680
DOI: 10.1080/10428194.2023.2185091

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.

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.NPM1^Mut MS may be genetically distinct from NPM1^Mut AML.NPM1^Mut MS may have inferior overall survival compared to NPM1^Mut 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

Substances

Nuclear Proteins
Nucleophosmin