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, Harvard Medical School, Boston, MA, USA. Beth Israel Deaconess Medical Center, Boston, MA, USA. North Bristol NHS Trust, Bristol, UK.
Leo P. Wu, Harvard Medical School, Boston, MA, USA. Beth Israel Deaconess Medical Center, Boston, MA, USA.
Christian Hirt, Harvard Medical School, Boston, MA, USA. Beth Israel Deaconess Medical Center, Boston, MA, USA.
German A. Pihan, Harvard Medical School, Boston, MA, USA. Beth Israel Deaconess Medical Center, Boston, MA, USA.
Sanjay S. Patel, Weill Cornell Medical College, New York, NY, USA.
Wayne Tam, Weill Cornell Medical College, New York, NY, USA.
Carlos E. Bueso-Ramos, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rashmi Kanagal-Shamanna, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Philipp W. Raess, Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
Alexa Siddon, Yale School of Medicine, New Haven, CT, USA.
Damodaran Narayanan, Harvard Medical School, Boston, MA, USA. Brigham and Women's Hospital, Boston, MA, USA.
Elizabeth A. Morgan, Harvard Medical School, Boston, MA, USA. Brigham and Women's Hospital, Boston, MA, USA.
Geraldine S. Pinkus, Harvard Medical School, Boston, MA, USA. Brigham and Women's Hospital, Boston, MA, USA.
Emily F. Mason, Vanderbilt University Medical Center, Nashville, TN, USA.
Eric D. Hsi, Wake Forest Baptist Health, Winston-Salem, NC, USA.
Heesun J. Rogers, Cleveland Clinic, Cleveland, OH, USA.
Laura Toth, Department of Pathology, The University of New Mexico, Albuquerque, NM, USA.
Kathryn Foucar, Department of Pathology, The University of New Mexico, Albuquerque, NM, USA.
Stephanie N. Hurwitz, Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA.
Adam Bagg, Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA.
Anton Rets, ARUP Laboratories, Salt Lake City, UT, USA. Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Tracy I. George, ARUP Laboratories, Salt Lake City, UT, USA. Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Attilio Orazi, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Daniel A. Arber, Department of Pathology, University of Chicago, Chicago, IL, USA.
Robert P. Hasserjian, Harvard Medical School, Boston, MA, USA. Massachusetts General Hospital, Boston, MA, USA.
Olga K. Weinberg, UT Southwestern Medical Center, Dallas, TX, USA.

Document Type

Article

Publication Date

5-1-2023

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.

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