Review Article

Primary Myelofibrosis: Current Concepts in Molecular Pathogenesis, Precision Diagnosis, and Emerging Therapeutic Strategies

Abstract

Primary myelofibrosis (PMF) is a clonal myeloproliferativ neoplasm characterized by bone marrow fibrosis, extramedullary hematopoiesis, and progressive cytopenias. Advances in molecular biology, diagnostic criteria, prognostic modeling, and targeted therapies have significantly improved the understanding of management of PMF. This review focused on the molecular pathogenesis, diagnostic criteria, prognostic scoring systems, therapeutic strategies, and precision medicine approach in PMF. A comprehensive literature search on molecular pathogenesis, clinical trials, prognostic models, and emerging therapies in PMF. Aberrant activation of the JAK-STAT pathway due to driver mutations (JAK2, CALR, MPI) and additional high-risk mutations promotes uncontrolled megakaryopoiesis, chronic inflammation, and fibrosis. The WHO 2022 and ICC 2022 criteria refined diagnostic accuracy through integrated morphological and molecular approaches. Molecular-based prognostic models such as MPSS70 + v2.0 and GIPSS provide superior risk stratification. JAK inhibitors (ruxotinib, fedratinib, pancritinib, mpmelotinib) remain central in symptom control and spleen reduction, Emerging therapies including telomerase inhibitors, BET inhibitors, and precision combinations show promising early results. Hematopoietic stem cell transplantation remains the only curative approach for eligible patients. Precision medicine integrating multi omics, AI, and real-world data is transforming PMF management. In recent times, PMF management has evolved toward molecularly guided, risk-adapted, and patient-centered core. The integration of advanced diagnostics, novel therapeutics, and precision approaches offers hope for improved survival and quality of life. 

Authors affiliation:

Francisca Obianuju Ndubuisi: Department of Medical Laboratory Sciences, Faculty of Health Science and Technology, University of Nigeria.
Silas Anayo Ufelle: Department of Medical Laboratory Sciences, Faculty of Health Science and Technology, University of Nigeria. 
Alphonsus Ogbonna Ogbuabor (ORCID): Department of Medical Laboratory Science, Faculty of Allied Health Sciences, Enugu State University of Science and Technology, Agbani, Nigeria. 

How To Cite: F.O. Ndubuisi, S.A. Ufelle, and A.O. Ogbuabor. Primary Myelofibrosis: Current Concepts in Molecular Pathogenesis, Precision Diagnosis, and Emerging Therapeutic Strategies. Journal of Public Health and Environmental Research, 2(2):72–80, 2026. https://doi.org/10.58612/jpher228