ISSN 2997-1036
International Journal of Hematology | Vol. 3, No. 9, September 2012 | pp. 65–72
DOI: 10.46882/2012/IJH/000033
Review Article
Title: Molecular landscape and targeted therapeutic inhibitors in myelofibrosis
Names of Authors: M. A. Bello¹, O. R. Eze²
Authors’ Affiliations: ¹Department of Haematology, Aminu Kano Teaching Hospital, Kano, Nigeria; ²Department of Pathology, University of Benin, Benin City, Nigeria
Abstract: Myelofibrosis is a clonal hematopoietic stem cell disorder characterized by bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly. This review synthesizes the molecular landscape of myelofibrosis, focusing on driver mutations in JAK2 (V617F), CALR, and MPL genes that induce constitutive activation of the JAK-STAT signaling pathway. The prognostic impact of high molecular risk mutations, including ASXL1, EZH2, and IDH1/2, is explored in relation to accelerated leukemic transformation. Therapeutic paradigms have shifted from supportive care toward targeted tyrosine kinase inhibitors. Small-molecule JAK1/JAK2 inhibitors like ruxolitinib demonstrate substantial efficacy in reducing spleen volume, suppressing inflammatory cytokine cascades, and improving constitutional symptoms. However, these agents often induce dose-dependent myelosuppression, requiring careful dose titration. Allogeneic hematopoietic stem cell transplantation remains the only curative strategy, but it is limited by high treatment-related mortality. Emerging combination protocols incorporating JAK inhibitors with bromodomain inhibitors or BCL-2 inhibitors represent the next frontier in reversing marrow fibrosis and eliminating neoplastic clones.
Keywords: Myelofibrosis, JAK2 mutation, ruxolitinib, JAK-STAT pathway, splenomegaly
Manuscript Timeline: Received: June 11, 2012; Revised: July 20, 2012; Accepted: August 10, 2012; Published: September 15, 2012