New Markers of Disease Progression in Myelofibrosis

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.

Keywords: chronic myeloproliferative neoplasms; inflammation; primary myelofibrosis; prognosis.

Figure 1

Summary of diagnostic WHO criteria for primary myelofibrosis (PMF) and prefibrotic myelofibrosis (pre-MF). Abbreviations: MK = megakaryocyte; LDH = lactate dehydrogenase; WHO = World Health Organization. Adapted from Arber et al. Blood 2016 [2] and Gowin et al. Leuk Res 2015 [15].

Figure 2

Summary of IWG diagnostic criteria for post polycythaemia myelofibrosis (post-PV MF) and post essential thrombocythemia myelofibrosis MF (post-ET MF). Abbreviations: Hb = hemoglobin; LDH = lactate dehydrogenase; PV = polycythemia vera; ET = essential thrombocythemia; BM = bone marrow; IWG = International Working Group. * Constitutional symptoms: >10% weight loss in 6 months, night sweats, and unexplained fever (>37.5 °C). Adapted from Arber et al. Blood 2016 [2] and Gowin et al. Leuk Res 2015 [15].