Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study

Yahya A. Al-Ghamdi, Department of Pathology, Umm Al-Qura University, Makkah, Saudi Arabia; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
Jonathan Lake, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Adam Bagg, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Beenu Thakral, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sa A. Wang, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Carlos Bueso-Ramos, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Lucia Masarova, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Srdan Verstovsek, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Heesun J. Rogers, Department of Pathology, University of Utah, Salt Lake City, Utah.
Eric D. Hsi, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Jonathon H. Gralewski, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Devon Chabot-Richards, Department of Pathology, University of New Mexico, Albuquerque, New Mexico.
Tracy I. George, Department of Pathology, University of Utah, Salt Lake City, Utah.
Anton Rets, Department of Pathology, University of Utah, Salt Lake City, Utah.
Robert P. Hasserjian, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Olga K. Weinberg, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
Megan Parilla, Department of Pathology, Loyola University, Maywood, Illinois.
Daniel A. Arber, Department of Pathology, University of Chicago, Chicago, Illinois.
Osvaldo Padilla, Department of Pathology, Texas Tech University Health Sciences Center, El Paso, Texas.
Attilio Orazi, Department of Pathology, Texas Tech University Health Sciences Center, El Paso, Texas.
Wayne Tam, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.Follow

Document Type

Article

Publication Date

3-1-2023

Abstract

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1 and SRSF2 comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.

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