骨髄増殖性疾患の遺伝子変異

Genetic abnormalities linked to myeloproliferative disorders

　慢性骨髄性白血病におけるBCR-ABLの形成をはじめとして，骨髄増殖性疾患ではJAK2，KITの変異，PDGFRA，PDGFRB，FGFR1とそれぞれのパートナー遺伝子との融合が見いだされてきた．これらの遺伝子異常は，リガンド非依存性のチロシンキナーゼの活性化および細胞の自律増殖をもたらし，骨髄増殖性疾患の発症原因となっている．さらに，JAK2変異の出現しやすさを規定する遺伝的背景，あるいはpre-JAK2変異と呼ぶべき遺伝子変異も同定され，骨髄増殖性疾患の分子病態が明らかにされつつある．

The generation of BCR-ABL fusion gene in CML, but also a gain-of-function mutation of JAK2, MPL, and KIT, and the rearrangement of PDGFRA, PDGFRB, and FGFR1 were detected in the majority of patients with myeloproliferative disorders. These mutations confer the cytokine-independent activation of tyrosine kinases and autosomal cell growth, and cause the development of myeloproliferative disorders. In addition to these abnormalities in tyrosine kinases, the discovery of TET2 mutation in myeloproliferative disorders, and the genetic background of JAK2 V617F shed light on the molecular basis of myeloproliferative disorders.