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M. Schino et al.
as an early predictive marker capable of precociously iden- tifying patients with an overt-myelofibrotic BM failure, could also select those patients that would benefit from precocious treatment.32
Our analysis not only supports the role of the MK and their activation in the evolution of PV and early/prefibrot- ic PMF, but also seems to suggest that, for the treatment of this neoplasia, as well as the inhibition of specific muta- tions, which may partially alter the natural history of the disease, the blockage of the fibrotic evolution and there- fore of its main key-player, the MK, should be a future therapeutic strategy to be investigated.30
M-ACT is also a very useful morphological parameter in the diagnostic phase of MPN. In fact, none of the ET patients showed M-ACT, which when present, identifies only an early/prefibrotic PMF.
Interestingly the M-ACT showed a significant lower incidence in triple-negative patients in comparison to those with a driver gene mutation (24.7% vs. 40.5%) rein- forcing the idea of a more indolent disease for this sub- group while maintaining its predictive role for the fibrotic evolution also in triple-negative patients.
In addition, M-ACT parameter evaluation represents an easily executable analysis with a high agreement index between pathologists. Moreover, the search for M- ACT in BM biopsies in the diagnostic phase of MPN patients can be performed widely without the need for further analysis such as immunohistochemistry or molecular analysis.
The main limitation of our study is the retrospective design, hence the time estimate of progression to overt myelofibrosis and the estimate of PFS based on the patient chart review can lack of accuracy. Moreover, the team physician remained the same over years and the cri-
teria for the diagnosing progression to overt myelofibro- sis were aligned with those of the IWG-MRT consen- sus.21
Although we analyzed a large cohort, the results of this single-center study need confirmation in other independ- ent MPN patient cohorts, and M-ACT should be validated as a prognostic tool.
Disclosures
The authors have no conflict of interest to disclose. The study was carried out in accordance with the Declaration of Helsinki and the consent for retrospective analysis of all clinical data, according to the Ethical Committee of the Catholic University School of Medicine, was obtained by all the patients at the hos- pital admission. The report does not present identifying images or other personal or clinical details of participants that compromise anonymity.
Contributions
LML, MS, VF and MM were the principal authors and the main contributors in writing the manuscript; ER, SB, VR, MDC and PC analyzed and interpreted the patient data; MM, LML, MS and VF performed the biopsies analysis; LML and VDS read and corrected the manuscript. All authors read and approved the final manuscript.
Acknowledgments
We thank Dr. Sara Capodimonti and Dr. Tonia Cenci for their technical support.
Funding
This study was supported by Università Cattolica del Sacro Cuore, Fondi d’Ateneo, Linea D1 (2018 and 2019; MM and LML).
References
1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J. WHO classi- fication of tumours of haematopoietic and lymphoid tissues (Revised 4th edition). IARC: Lyon 2017.
2. Murphy S. Diagnostic criteria and progno- sis in polycythemia vera and essential thrombocythemia. Semin Hematol. 1999;36(1 Suppl 2):S9-13.
3. Georgii A, Buesche G, Kreft A. The histopathology of chronic myeloprolifera- tive diseases. Baillieres Clin Haematol. 1998;11(4):721-749.
4. Barbui T, Thiele J, Gisslinger H, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discus- sion. Blood Cancer J. 2018;8(2):15.
5. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901.
6. Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to pre- dict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703-1708.
7. Gangat N, Caramazza D, Vaidya R, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for
primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29(4):392-397.
8. Rumi E, Cazzola M. Diagnosis, risk stratifi- cation, and response evaluation in classical myeloproliferative neoplasms. Blood. 2017;129(6):680-692.
9.Grinfeld J, Nangalia J, Baxter EJ et al. Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med. 2018;379(15):1416-1430.
10. Guglielmelli P, Lasho TL, Rotunno G, et al. MIPSS70: mutation-enhanced international prognostic score system for transplanta- tion-age patients with primary myelofibro- sis. J Clin Oncol. 2018;36(4):310-318.
11. Tefferi A, Guglielmelli P, Lasho TL, et al. MIPSS70+ Version 2.0: mutation and kary- otype-enhanced international prognostic scoring system for primary myelofibrosis. J Clin Oncol. 2018;36(17):1769-1770.
12. Tefferi A, Guglielmelli P, Nicolosi M, et al. GIPSS: genetically inspired prognostic scor- ing system for primary myelofibrosis. Leukemia. 2018;32(7):1631-1642.
13. Tefferi A, Guglielmelli P, Lasho TL, et al. Mutation-enhanced international prognos- tic systems for essential thrombocythaemia and polycythaemia vera. Br J Haematol. 2020;189(2):291-302.
14.Larocca LM, Heller PG, Podda G, et al. Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome. Platelets. 2015;26 (8):751-757.
15. Schmitt A, Jouault H, Guichard J, Wendling F, Drouin A, Cramer EM. Pathologic inter- action between megakaryocytes and poly- morphonuclear leukocytes in myelofibro- sis. Blood. 2000;96(4):1342-1347.
16. Centurione L, Di Baldassarre A, Zingariello M, et al. Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1(low) mice. Blood. 2004;104(12):3573-3580.
17. Yan XQ, Lacey D, Hill D, et al. A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin (mpl ligand): reversal of disease by bone marrow transplantation. Blood. 1996;88(2): 402-409.
18. Gianelli U, Iurlo A, Vener C, et al. The sig- nificance of bone marrow biopsy and JAK2V617F mutation in the differential diagnosis between the "early" prepoly- cythemic phase of polycythemia vera and essential thrombocythemia. Am J Clin Pathol. 2008;130(3):336-342.
19. Ridgeway JA, Tinsley S, Kurtin SE. Practical guide to bone marrow sampling for sus- pected myelodysplastic syndromes. J Adv Pract Oncol. 2017;8(1):29-39.
20. De Stefano V, Ruggeri M, Cervantes F, et al. High rate of recurrent venous thromboem- bolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia. 2016; 30(10):2032-2038.
21.
Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-poly-
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