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Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study
Yahya A Al-Ghamdi1, Jonathan Lake2, Adam Bagg2
1Department of Pathology, Umm Al-Qura University, Makkah, Saudi Arabia; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
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.
Insights
Triple-negative primary myelofibrosis (TN-PMF) presents distinct characteristics from mutation-driven PMF. TN-PMF shows differences in blood counts, bone marrow findings, and specific genetic mutations like ASXL1/SRSF2 comutations.
Area of Science:
- Hematology
- Oncology
- Molecular Genetics
Background:
- Primary myelofibrosis (PMF) is a myeloproliferative neoplasm often driven by JAK2, CALR, or MPL mutations.
- Triple-negative PMF (TN-PMF) lacks these common driver mutations, and its characteristics are less understood.
- Understanding TN-PMF is crucial for accurate diagnosis and potential therapeutic strategies.
Purpose of the Study:
- To investigate the clinicopathologic and molecular genetic distinctions between TN-PMF and PMF with driver mutations (DM-PMF).
- To identify unique features of TN-PMF that may differentiate it from DM-PMF.
Main Methods:
- Comparative analysis of 56 TN-PMF patients and 89 DM-PMF patients meeting 2016 WHO criteria.
- Evaluation of clinical data, bone marrow morphology, cytogenetics, and targeted next-generation sequencing for mutations.
Main Results:
- TN-PMF patients exhibited higher rates of thrombocytopenia and lower rates of organomegaly compared to DM-PMF.
- Bone marrow analysis revealed fewer granulocytic elements and more dyserythropoiesis in TN-PMF.
- Cytogenetic analysis showed increased trisomy 8, and molecular profiling indicated lower ASXL1 mutation frequency but enriched ASXL1/SRSF2 comutations in TN-PMF.
Conclusions:
- Significant clinicopathologic and molecular differences exist between TN-PMF and DM-PMF.
- The distinct mutation profile in TN-PMF, particularly ASXL1/SRSF2 comutations, suggests potential unique pathogenic mechanisms.
- These findings may have implications for the prognosis and management of TN-PMF.
