文章：

MR-1通过MEK去磷酸化，阻断巨核细胞的分化和CML从慢性期向母细胞危象的转变

MR-1 blocks the megakaryocytic differentiation and transition of CML from chronic phase to blast crisis through MEK dephosphorylation

原文发布日期：2013-03-29

DOI: 10.1038/bcj.2013.5

类型: Original Article

开放获取: 是

英文摘要：

Chronic myelogenous leukemia (CML) evolves from a chronic phase characterized by the Philadelphia chromosome as the sole genetic abnormality and the accumulation of mature cells in peripheral blood into blast crisis, which is characterized by the rapid expansion of myeloid- or lymphoid-differentiation-arrested blast cells. Although ample studies have been conducted on the disease progress mechanisms, the underlying molecular mechanisms of the malignant phenotype transition are still unclear. In this study, we have shown that myofibrillogenesis regulator-1 (MR-1) was overexpressed in blast crisis patients and leukemic cells, but there was little trace expressed in healthy individuals and in most patients in CML chronic phase. MR-1 could inhibit the differentiation of myeloid cells into megakaryocytic lineages and accelerate cell proliferation. The molecular mechanism responsible for these effects was the interaction of MR-1 with MEK, which blocked the MEK/ERK signaling pathway by dephosphorylating MEK. Our results provide compelling and important evidence that MR-1 might act as a diagnostic marker and potential target of CML progression from chronic phase to blast crisis.

摘要翻译： 

慢性粒细胞白血病（CML）从慢性期进展为急变期的过程，其慢性期以费城染色体为唯一遗传异常及外周血成熟细胞积聚为特征，而急变期则表现为髓系或淋巴系分化受阻的原始细胞快速扩增。尽管已有大量研究探讨疾病进展机制，但恶性表型转变的潜在分子机制仍不明确。本研究发现，肌纤维生成调节因子-1（MR-1）在急变期患者及白血病细胞中过度表达，而在健康个体及多数CML慢性期患者中几乎无表达。MR-1能抑制髓系细胞向巨核细胞系分化并加速细胞增殖，其分子机制是通过与MEK相互作用，使MEK去磷酸化从而阻断MEK/ERK信号通路。我们的研究结果提供了有力证据，表明MR-1可作为CML从慢性期向急变期进展的诊断标志物及潜在治疗靶点。

原文链接：

MR-1 blocks the megakaryocytic differentiation and transition of CML from chronic phase to blast crisis through MEK dephosphorylation