骨髄増殖性疾患の概念

Current concept of myeloproliferative disorder

　骨髄増殖性疾患は，造血幹細胞レベルの細胞に遺伝子異常が起こり，分化能を有する複数の系統の骨髄系細胞がクローナルに過剰増殖する疾患群であり，しばしば病型間の移行もみられる．高齢者に多く発症し，経過は緩徐であるが，一部の症例は急性骨髄性白血病へと移行する．その原因のほとんどは染色体転座や点突然変異などによるチロシンキナーゼの恒常的活性化であり，真性多血症のほとんどの症例，本態性血小板血症，原発性骨髄線維症の約半数の症例でJAK2の，慢性骨髄性白血病ではBCR-ABLの活性化変異が認められる．

Myeloproliferative disorders(MPDs), including polycythemia vera(PV), essential thrombocytosis(ET), primary myelofibrosis(PMF), and several other diseases, are clonal disorders that derive from gene alterations at the level of hematopoietic stem cells.　MPDs are characterized by hyperproliferation of myeloid cells, which have an ability to terminally differentiate.　The JAK2 V617F mutation is found in the majority of PV and in about half of the cases with ET and PMF.　Also, BCR-ABL is a causative gene for chronic myeloid leukemia, and FIF1L1-PDGFRA for chronic eosinophilic leukemia.　So, it is considered that MPDs are caused by oncogenic tyrosine kinases, but other gene mutations are also supposed to be involved in their pathogenesis.