文章：

MLF2丝氨酸24位点磷酸化在BCR-ABL白血病发生中的作用

The role of phosphorylation of MLF2 at serine 24 in BCR-ABL leukemogenesis 

原文发布日期：2019-12-12 

英文摘要：

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder defined by the presence of the fusion gene BCR-ABL1 in primitive hematopoietic progenitors. The myeloid leukemia factors (MLFs) were identified in the fly and human, and are involved in acute leukemia and enhancing the myeloid factor; however, the function of MLF2 in CML is poorly understood. In this study, we demonstrated that MLF2 may play an oncogenic role in CML. The expression level of MLF2 was related to the proliferation, colony-formation ability, and sensitivity to imatinib in K562 cells. Moreover, phosphorylation at serine 24, detected through Phos-tag sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was required to maintain the activity of MLF2 in CML. The effects of MLF2 overexpression on the colony-formation ability in vitro and mouse survival in vivo could be alleviated by point mutation of MLF2 at serine 24. These findings uncover the oncogenic role of MLF2 through phosphorylation at serine 24 and provide a novel therapeutic target in CML. 

摘要翻译： 

慢性粒细胞白血病（CML）是一种以原始造血祖细胞中存在BCR-ABL1融合基因为特征的骨髓增殖性肿瘤。髓系白血病因子（MLFs）在果蝇和人类中被发现，参与急性白血病进程并增强髓系因子功能，然而MLF2在CML中的作用机制尚不明确。本研究证实MLF2可能在CML中发挥促癌作用：在K562细胞中，MLF2的表达水平与细胞增殖能力、集落形成能力以及对伊马替尼的敏感性密切相关。通过Phos-tag SDS-PAGE电泳技术检测发现，丝氨酸24位点的磷酸化对维持MLF2在CML中的活性至关重要。将MLF2丝氨酸24位点进行点突变后，可显著减弱MLF2过表达对体外集落形成能力及小鼠体内存活率的影响。这些发现揭示了MLF2通过丝氨酸24位点磷酸化发挥促癌作用的机制，为CML治疗提供了新的靶点。

原文链接：

The role of phosphorylation of MLF2 at serine 24 in BCR-ABL leukemogenesis