Simple Summary
Disease progression and prognosis in PMF are usually associated with worsening of anemia, increase of circulating blasts, and, more recently, with the presence, in addition to the “classical” driver mutations, of JAK2, MPL, and CALR genes, as well as of cytogenetic and molecular abnormalities that have been incorporated into new genetically based prognostic scoring systems. We have recently focused our attention on new biological markers of the disease, namely sIL-2Rα, eNAMPT, and CXCR4 expression on circulating CD34+ cells and CCL2 and VEGF-A polymorphisms, which have turned out to be associated with disease evolution and patient survival. Here, we discuss the role that recently described biological markers of the disease play in PMF progression and prognosis.
Abstract
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm due to the clonal proliferation of a hematopoietic stem cell. The vast majority of patients harbor a somatic gain of function mutation either of JAK2 or MPL or CALR genes in their hematopoietic cells, resulting in the activation of the JAK/STAT pathway. Patients display variable clinical and laboratoristic features, including anemia, thrombocytopenia, splenomegaly, thrombotic complications, systemic symptoms, and curtailed survival due to infections, thrombo-hemorrhagic events, or progression to leukemic transformation. New drugs have been developed in the last decade for the treatment of PMF-associated symptoms; however, the only curative option is currently represented by allogeneic hematopoietic cell transplantation, which can only be offered to a small percentage of patients.
Disease prognosis is based at diagnosis on the classical International Prognostic Scoring System (IPSS) and Dynamic-IPSS (during disease course), which comprehend clinical parameters; recently, new prognostic scoring systems, including genetic and molecular parameters, have been proposed as meaningful tools for a better patient stratification. Moreover, new biological markers predicting clinical evolution and patient survival have been associated with the disease. This review summarizes basic concepts of PMF pathogenesis, clinics, and therapy, focusing on classical prognostic scoring systems and new biological markers of the disease.
