的苯丙氨酸354亮氨酸多态性是细胞遗传学正常的急性髓系白血病的一个潜在预后因素。 （注：原文中“Is a Potential Prognostic Factor for Cytogenetically Normal Acute Myeloid Leukemia.”前面缺少具体基因或蛋白等相关主语，译文根据语境尽量补充完整使其符合逻辑）
Phe354Leu Polymorphism of Is a Potential Prognostic Factor for Cytogenetically Normal Acute Myeloid Leukemia.
作者信息
Yang Ming-Yu, Hsiao Hui-Hua, Liu Yi-Chang, Hsu Cheng-Ming, Lin Sheng-Fung, Lin Pai-Mei
机构信息
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, R.O.C.
Departments of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C.
出版信息
In Vivo. 2017 Sep-Oct;31(5):841-847. doi: 10.21873/invivo.11137.
BACKGROUND/AIM: Liver kinase B1 (LKB1) is a major activator of the AMP-dependent kinase/mammalian target of rapamycin pathway. The prevalence and the specificity of LKB1 gene mutation in acute myeloid leukemia (AML) have not been well established. This study aimed to examine mutation of LKB1 in AML and its clinical and pathological implications.
PATIENTS AND METHODS
Eighty-five patients newly diagnosed with cytogenetically normal AML were analyzed using polymerase chain reaction followed by direct sequencing.
RESULTS
A silent mutation (837C>T) of LKB1 was detected in one patient and a pathogenic polymorphism Phe354Leu which diminishes LKB1 ability to maintain cell polarity was detected in six (7%) patients. The Phe354Leu polymorphism occurred concurrently with mutations of nucleophosmin 1 (NPM1), fms-related tyrosine kinase 3 (FLT3) and CCAAT/enhancer binding protein alpha (CEBPA), but not with metabolism-related genes, isocitrate dehydrogenase [nicotinamide adenine dinucleotide phosphate (+)]1 (IDH1) and IDH2. Patients with Phe354Leu polymorphism diagnosed at younger ages had a worse overall survival.
CONCLUSION
LKB1 may be involved in the leukemogenesis and progression of cytogenetically normal AML.
背景/目的：肝脏激酶B1（LKB1）是AMP依赖激酶/雷帕霉素哺乳动物靶标通路的主要激活剂。急性髓系白血病（AML）中LKB1基因突变的发生率和特异性尚未完全明确。本研究旨在检测AML中LKB1的突变情况及其临床和病理意义。
患者与方法
对85例新诊断的细胞遗传学正常的AML患者采用聚合酶链反应及直接测序进行分析。
结果
1例患者检测到LKB1的沉默突变（837C>T），6例（7%）患者检测到致病性多态性Phe354Leu，该多态性会降低LKB1维持细胞极性的能力。Phe354Leu多态性与核磷蛋白1（NPM1）、fms相关酪氨酸激酶3（FLT3）和CCAAT/增强子结合蛋白α（CEBPA）的突变同时出现，但与代谢相关基因异柠檬酸脱氢酶[烟酰胺腺嘌呤二核苷酸磷酸（+）]1（IDH1）和IDH2的突变不同时出现。诊断时具有Phe354Leu多态性的年轻患者总生存期较差。
结论
LKB1可能参与细胞遗传学正常的AML的白血病发生和进展。
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