Title:Current and Emerging Therapies in Primary Myelofibrosis
Volume: 12
Issue: 1
Author(s): Sabarish Ayyappan, Murali Janakiram and Radha Raghupathy
Affiliation:
Keywords:
HDAC inhibitors, Hypomethylating agents, Interferon α, JAK2, mTOR inhibitors, Myelofibrosis, Targeted
therapies, fibrosis, myeloproliferative neoplasm
Abstract: Primary myelofibrosis is a clonal hematopoietic disorder characterized by ineffective hematopoiesis and
progressive bone marrow fibrosis. Patients with high risk myelofibrosis as determined by their advanced age, degree of
anemia, leukocytosis, constitutional symptoms and high percentage of circulating blasts have a very short median survival of
2 years. In addition quality of life is significantly compromised due to cytokine induced constitutional symptoms, frequent
transfusion for cytopenias and bulky splenomegaly. Progression to myelogenous leukemia occurs in about 20% of patients
within 10 years of diagnosis and is often fatal. Allogeneic hematopoietic transplantation is the only curative therapy but is
limited by patient eligibility, transplant related mortality and graft versus host disease. Androgens, erythropoietin
analogues, hydroxyurea, alkylators and spleen directed therapies have all been used with limited efficacy and no curative
potential. The discovery of mutations in the hematopoietic progenitors of patients with myelofibrosis, including the JAK2
V617F mutation and others has greatly improved our understanding of the disease and facilitated development of newer
targeted therapies. Our article will review new discoveries in the pathogenesis of myelofibrosis and focus on emerging
targeted treatments. These novel therapies including oral JAK2 inhibitors, immunomodulators, as well as inhibitors of
HDAC and mTOR, in isolation and in combination are likely to improve outcomes in management of this disease.
