Harada Hironori, Harada Yuka, Kimura Akiro
Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University.
Nihon Rinsho. 2009 Oct;67(10):1901-5.
Little was known about the mechanisms for myeloproliferative diseases (MPD) until 2005 when an activating mutation in the JAK2 tyrosine kinase (JAK2 V617F) was identified in >95% of patients with polycythemia vera (PV), and in a significant proportion of patients with essential thormbocythemia (ET) and primary myelofibrosis (PMF). Furthermore, activating abnormalities of some tyrosine kinases were identified in MPD and related diseases, suggesting that constitutive activation of the signaling pathway is a unifying feature of these diseases. On the other hand, the molecular mechanism of myelodysplastic syndromes (MDS) is still poorly understood. Recent study revealed that two types of AML1/RUNX1 mutants function via distinct molecular mechanisms to produce mutant-specific phenotypes of MDS. The mechanisms of MPD and MDS gradually become clear.
直到2005年,人们对骨髓增殖性疾病(MPD)的发病机制仍知之甚少。当时,在超过95%的真性红细胞增多症(PV)患者以及相当一部分原发性血小板增多症(ET)和原发性骨髓纤维化(PMF)患者中,发现了JAK2酪氨酸激酶的激活突变(JAK2 V617F)。此外,在MPD及相关疾病中还发现了一些酪氨酸激酶的激活异常,这表明信号通路的组成性激活是这些疾病的一个共同特征。另一方面,骨髓增生异常综合征(MDS)的分子机制仍知之甚少。最近的研究表明,两种类型的AML1/RUNX1突变体通过不同的分子机制发挥作用,从而产生MDS的突变特异性表型。MPD和MDS的机制逐渐变得清晰。