Advanced Molecular Diagnosis of Primary Myelofibrosis: A Review

Abstract

Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, anaemia, constitutional symptoms, and extramedullary haematopoiesis. As a clonal haematopoietic stem cell disorder, it is often accompanied by a disease-initiating driver mutation and shortened survival. Diagnosis is often based on bone marrow findings. Diagnosis is supported by the presence of janus kinase 2 (JAK2), calreticulin (CALR), or thrombopoietin receptor protein (MPL) mutation, found in approximately 90% of patients, is supportive but not essential for diagnosis; these mutations are also prevalent in the closely related MPNs, namely polycythemia Vera (PV) and essential thrombocythemia (ET). Diagnosis of PMF is based upon the 2016 WHO criteria and includes a combination of clinical and laboratory findings. Patients with pre PMF often present with thrombocytosis (increased platelet count) and a lack of bone marrow fibrosis, thus they were often misdiagnosed as having ET. In ET patients, the differentiating bone marrow findings include granulocytic and erythropoietic cells that are in regular ratio with normal megakaryocytes. In Pre-PMF. Anaemia may be present, however tear-drop red blood cells (RBCs) are rare. The 2016 World Health Organization classification system distinguishes “prefibrotic” from “overtly fibrotic” PMF; the former might mimic ET in its presentation. Furthermore, approximately 15% of patients with ET or PV might progress into a PMF-like phenotype (post-ET/PV MF) during their clinical course.