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Introduction
Primary myelofibrosis (PMF) is a classic myeloproliferative neoplasm (MPN), characterized by the appearance of diffuse fibrous tissue in the bone marrow, increased numbers of myeloid cells, extramedullary hematopoiesis, organomegaly, pancytopenia and an altered cytokine expression profile (1-4). PMF comprises chronic and acute PMF (CPMF and APMF, respectively), according to the type of onset.
The majority of PMF cases are hard to identify and diagnose during the asymptomatic state (5). PMF-related mortality is often caused by cardiac failure, infection, hemorrhage or acute leukemia transformation (6). Acute leukemia transformation occurs in ~20% of PMF patients within 10 years of diagnosis (3). PMF is difficult to cure, and the only known treatment method is allogeneic stem cell transplantation (7). PMF is a severe disease that poses a serious threat to human health. The median survival time of PMF is 3.5-5.5 years from diagnosis (8,9), and the 10-year survival rate for familial PMF cases is only 30% (10). PMF predominantly occurs in patients aged >50 years. However, half of the children with PMF are diagnosed at <3 years old (1). Familial PMF cases account for ~7.6% of chronic myeloproliferative disorders (11). The first-degree relatives of patients with PMF have a 5-7-fold increased risk of developing MPN, as compared with other more distant relatives (10). Janus kinase 2 (JAK2) belongs to the identified Janus family of non-receptor tyrosine kinases that are important for the transduction of cytokine-mediated signals in several cell types (2). The JAK2 V617F somatic mutation arises from a single base G-T transversion in the pseudokinase domain of JAK2. The somatic mutation is observed in 50% of cases with PMF. This mutation results in a valine-to-phenylalanine substitution at codon 617(12), leading to constitutive kinase activation (13). The JAK2 V617F mutation stimulates various signaling pathways downstream of JAK2, thus leading to cytokine-independent cell survival and proliferation (14). A previous study showed that the rate of splenomegaly in JAK2 V617F-mutated PMF patients was higher than that in JAK2-negative PMF patients, whereas the incidence of leukemia transformation was lower in JAK2 V617F-mutated PMF than in JAK2-negative patients (15).
Since the reports of familial PMF are infrequent, the present case report describes two familial cases (two sisters) with PMF, both of whom carried a JAK2 V617F mutation. Both sisters provided written...