慢性骨髄増殖性疾患の白血病幹細胞

Leukemic stem cells in chronic myeloproliferative diseases

慢性骨髄増殖性疾患は，複数系統の血球が増加，肝脾腫を伴う，相互に病型移行がみられる，などの共通した特徴を有する造血幹細胞疾患である．染色体転座による融合遺伝子の形成や遺伝子変異により，通常は刺激に応じて活性化されるチロシンキナーゼが恒常的に活性化されて発症する．慢性骨髄増殖性疾患の腫瘍細胞は，少数の白血病幹細胞と大多数の分化した腫瘍細胞から構成されており，その白血病幹細胞は，正常造血幹細胞と同様なKLS分画に濃縮される．Wnt/βカテニンシグナル，ヘッジホッグシグナル，promyelocytic leukemia protein(PML)，フォークヘッド転写因子(FOXO)など，正常造血幹細胞の自己複製や維持に必須な分子により，白血病幹細胞も維持，制御されている．

Chronic myeloproliferative disease (which were termed myeloproliferative neoplasms (MPN) in the revised 2008 WHO classification) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more of the myeloid lieage cells, and hepatosplenomegaly.　The generation of the fusion gene by translocation or a gain-of-function mutation of tyrosine kinase constantly activate their kinase activity, and induce MPN.　MPN cells are composed of a very small number of leukemic stem cells (LSC) and a vast majority of differentiated leukemic cells.　LSCs in MPN are enriched in the fraction of c-Kit^＋lineage^－Sca-1^＋ cells, as are normal hematopoietic stem cells.　The essential molecules for self-renewal and maintenance of normal hematopoietic stem cells also play an important role in the maintenance and regulation of LSCs in MPN.