Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Leuk Lymphoma. 2013 Aug;54(8):1614-25. doi: 10.3109/10428194.2012.749402. Epub 2012 Dec 24.
Abstract Several molecular markers, such as NPM1, FLT3 and CEBPA, have been incorporated into both the World Health Organization and European LeukemiaNet classifications as routine assessments for the diagnosis and evaluation of prognostic significance in acute myeloid leukemia (AML). Lipocalin 2 (LCN2) is related to cancer development and is believed to be associated with the outcome of cytogenetically normal (CN)-AML. In the present study, we analyzed the prognostic effects and interactions of LCN2 expression (by molecular analysis, quantitative real-time polymerase chain reaction [qRT-PCR]) with neucleophosmin 1, fms-related tyrosine kinase 3 (FLT3) and CCAAT/enhancer-binding protein alpha mutations in 85 patients with CN-AML receiving intensive induction chemotherapy. Our results indicate that patients with higher LCN2 mRNA expression in the bone marrow (LCN2high), especially in combination with wild type FLT3-ITD, had better prognoses. FLT3-ITD compensated LCN2-overexpression-enhanced oxidative stress-induced apoptosis in cell line studies. In conclusion, LCN2high was associated with better prognosis, and FLT3 status had an adjuvant effect on overall survival.
摘要 几种分子标志物,如 NPM1、FLT3 和 CEBPA,已被纳入世界卫生组织和欧洲白血病网络分类中,作为急性髓细胞白血病(AML)诊断和评估预后意义的常规评估。脂联素 2(LCN2)与癌症的发生有关,据信与核型正常(CN)-AML 的结果有关。在本研究中,我们分析了 85 例接受强化诱导化疗的 CN-AML 患者中 LCN2 表达(通过分子分析、实时定量聚合酶链反应[qRT-PCR])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突变的预后作用和相互作用。我们的结果表明,骨髓中 LCN2 mRNA 表达较高(LCN2high)的患者,尤其是与野生型 FLT3-ITD 相结合的患者,预后较好。FLT3-ITD 在细胞系研究中补偿了 LCN2 过表达增强的氧化应激诱导的细胞凋亡。总之,LCN2high 与较好的预后相关,FLT3 状态对总生存有辅助作用。