Polycythemia vera: the current status of preclinical models and therapeutic targets

Introduction: Polycythemia vera (PV) is the most common myeloproliferative neoplasm (MPN). PV is characterized by erythrocytosis, leukocytosis, thrombocytosis, increased hematocrit, and hemoglobin in the peripheral blood. Splenomegaly and myelofibrosis often occur in PV patients. Almost all PV patients harbor a mutation in the JAK2 gene, mainly represented by the JAK2(V617F) point mutation. Areas covered: This article examines the recent in vitro and in vivo available models of PV and moreover, it offers insights on emerging biomarkers and therapeutic targets. The evidence from mouse models, resembling a PV-like phenotype generated by different technical approaches, is discussed. The authors searched PubMed, books, and clinicaltrials.gov for original and review articles and drugs development status including the terms Myeloproliferative Neoplasms, Polycythemia Vera, erythrocytosis, hematocrit, splenomegaly, bone marrow fibrosis, JAK2(V617F), Hematopoietic Stem Cells, MPN cytoreductive therapy, JAK2 inhibitor, histone deacetylase inhibitor, PV-like phenotype, JAK2(V617F) BMT, transgenic JAK2(V617F) mouse, JAK2 physiologic promoter. Expert opinion: Preclinical models of PV are valuable tools for enabling an understanding of the pathophysiology and the molecular mechanisms of the disease. These models provide new biological insights on the contribution of concomitant mutations and the efficacy of novel drugs in a 'more faithful' setting. This may facilitate an enhanced understanding of pathogenetic mechanisms and targeted therapy.