原発性骨髄線維症

Pathogenesis and clinical features―recent progress in research：primary myelofibrosis

　原発性骨髄線維症は，造血幹細胞レベルで生じた遺伝子異常により，クローナルな骨髄系細胞増殖をきたし，異常クローン由来の巨核球や単球などからの増殖因子・サイトカインの産生によって骨髄間質細胞の増殖から，骨髄の広範な線維化，骨硬化，血管新生などを生じる．その結果，無効造血や，末梢血での涙滴状赤血球の出現，白赤芽球症，髄外造血による巨脾などの臨床症状を呈する．2005年に骨髄増殖性腫瘍において共通のJAK2チロシンキナーゼの遺伝子変異による活性化が報告され，疾患の本態の解明が急速に進んでいる．疾患の進展につながる分子細胞学的な病態解明が，今後の分子標的療法などの有効な治療法の開発につながると期待される．

Primary myelofibrosis(PMF)is a clonal myeloproliferative neoplasm characterized by the proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that is associated with bone marrow fibrosis, osterosclerosis, angiogenesis, and extramedullary hematopoiesis. Recently, activated JAK2 mutation(V617F), which is involved in cytokine receptor signaling, and MPL(receptor for thrombopoietin)were discovered in about half or about 5% of PMF patients, respectively. Multiple studies indicate that these mutational events originate in a hematopoietic stem cell, and PMF is considered as a clonal stem cell disorder. Understanding of the cellular and molecular events that lead to the development of PMF is expected to provide the opportunity for targeted therapies for PMF.