Ming-Yu Yang1,2, Hui-Hua Hsiao3,4, Yi-Chang Liu3,4, Cheng-Ming Hsu5,6, Sheng-Fung Lin7,4, Pai-Mei Lin8. 1. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, R.O.C. 2. Departments of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C. 3. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C. 4. Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. 5. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan, R.O.C. shlin@cc.kmu.edu.tw scm0031@cgmh.org.tw paimei@isu.edu.tw. 6. Department of Otolaryngology, Chiayi Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Chiayi, Taiwan, R.O.C. 7. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C. shlin@cc.kmu.edu.tw scm0031@cgmh.org.tw paimei@isu.edu.tw. 8. Department of Nursing, I-Shou University, Kaohsiung, Taiwan, R.O.C. shlin@cc.kmu.edu.tw scm0031@cgmh.org.tw paimei@isu.edu.tw.
Abstract
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. Copyright
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. Copyright
Authors: H Kiyoi; T Naoe; Y Nakano; S Yokota; S Minami; S Miyawaki; N Asou; K Kuriyama; I Jinnai; C Shimazaki; H Akiyama; K Saito; H Oh; T Motoji; E Omoto; H Saito; R Ohno; R Ueda Journal: Blood Date: 1999-05-01 Impact factor: 22.113
Authors: V Launonen; E Avizienyte; A Loukola; P Laiho; R Salovaara; H Järvinen; J P Mecklin; A Oku; M Shimane; H C Kim; J C Kim; J Nezu; L A Aaltonen Journal: Cancer Res Date: 2000-02-01 Impact factor: 12.701