原発性骨髄線維症

Treatment―guideline, outcome, prognosis：primary myelofibrosis

　原発性骨髄線維症は平均生存期間3～5年の難治進行性疾患であり，血球減少に伴う感染症や出血，脾腫，白血化，門脈圧亢進などを主要な臨床像とする病態である．その治療は症状軽減のための対症療法と根治を目的とした同種造血幹細胞移植に大別される．しかし，最近ではJAK2 V617Fに代表されるJAK/STAT経路を恒常的に活性化する遺伝子変異が一部の症例において病態の根幹をなすことが示され，多くの分子標的治療薬が臨床研究の段階に躍進した．本稿では，原発性骨髄線維症における対症療法の意義・同種造血幹細胞移植成績と適応，そして新規治療薬の現状につき概説する．

Primary myelofibrosis is a clonal myeloproliferative neoplasm characterized by anemia, marked splenomegaly, and bone marrow fibrosis. Median survival time is estimated at 3-5 years, and causes of deaths include leukemic transformation and consequences of progressive cytopenia. Treatment remains largely palliative with the exception of allogeneic stem cell transplantation, which is the only curative approach in some patients. However, the identification of the JAK2 V617F mutation in more than half of the patients may improve our understanding of the disease biology, and clinical phase Ⅰ/Ⅱ trials of the drugs targeting this mutation or the associated molecular abnormalities are currently underway. In this review we will update the current therapeutic options as well as the development of innovative molecular targeting agents for primary myelofibrosis.