Wang Xiang, Ling Bing-Qian, Dai Mei-Fang, Wang Xing-Bing
Department of Hematology, Anhui Provincial Hospital Affiliated to Anhui Medical University,Hefei 230000, Anhui Province, China.
College of Life Sciences, University of Science and Technology of China,Hefei 230000, Anhui Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Aug;27(4):1046-1052. doi: 10.19746/j.cnki.issn.1009-2137.2019.04.009.
To investigate the relationship between the expression of lysosomal membrane proteins LAMP1, TPC1 and TPC2 in acute myeloid leukemia (AML) cells and clinical indications of AML and to explore the possible role in the genesis and development of AML and clinical significance.
Real-time quantitative PCR was used to detect the mRNA expression of LAMP1, TPC1 and TPC2 in AML cell lines (HL-60, NB4) and 57 patients with acute myeloid leukemia (including 44 initially treated patients and 13 relapsed and refractory patients). The relationship of mRNA expression levels with clinical indicators and post-chemotherapy remission was analyzed.
Compared with CD34 hematopoietic stem cells (HSC), the expression levels of LAMP1 and TPC1 in AML cell lines HL-60 and NB4 significantly increased, while the expression level of TPC2 was not significantly different. The expression levels of LAMP1, TPC1 and TPC2 in bone marrow mononuclear cells (BMMNC) of AML patients were higher than those in normal human BMMNC (P<0.05), and the expression levels of LAMP1, TPC1 and TPC2 in CD34 primary AML cells(CD34 primary cells in the patient's bone marrow >90%) were also high. There was no significant difference in the expression of LAMP1, TPC1 and TPC2 between CD34HSC of patients with AML and relapsed/refractory patients (P>0.05). No correlation was found between age, sex and genotype and expression of membrane proteins (P>0.05). The expression levels of LAMP1 and TPC1 positively correlated with the number of white blood cells in peripheral blood of patients (P<0.01). LAMP1 and TPC2 were found to be associated with remission after a course of chemotherapy in newly diagnosed patients. Initially treated patients with high expression of LAMP1 in the bone marrow not easily relieved after one course of chemotherapy. Patients with high expression of TPC2 in the bone marrow more likely to be relieved after one course of chemotherapy.
The mRNA of the three membrane proteins are highly expressed in AML patients, and LAMP1 and TPC1 are risk factors for AML disease progression. High expression of TPC2 is beneficial for chemotherapy of patients with newly diagnosed AML.
探讨溶酶体膜蛋白LAMP1、TPC1和TPC2在急性髓系白血病（AML）细胞中的表达与AML临床指标的关系，探讨其在AML发生发展中的可能作用及临床意义。
采用实时定量PCR检测AML细胞系（HL-60、NB4）及57例急性髓系白血病患者（包括44例初治患者和13例复发难治患者）中LAMP1、TPC1和TPC2的mRNA表达。分析mRNA表达水平与临床指标及化疗后缓解情况的关系。
与CD34造血干细胞（HSC）相比，AML细胞系HL-60和NB4中LAMP1和TPC1的表达水平显著升高，而TPC2的表达水平无显著差异。AML患者骨髓单个核细胞（BMMNC）中LAMP1、TPC1和TPC2的表达水平高于正常人BMMNC（P<0.05），CD34原代AML细胞（患者骨髓中CD34原代细胞>90%）中LAMP1、TPC1和TPC2的表达水平也较高。AML患者与复发/难治患者的CD34HSC中LAMP1、TPC1和TPC2的表达无显著差异（P>0.05）。未发现年龄、性别、基因型与膜蛋白表达之间存在相关性（P>0.05）。LAMP1和TPC1的表达水平与患者外周血白细胞数量呈正相关（P<0.01）。发现LAMP1和TPC2与新诊断患者一个疗程化疗后的缓解情况有关。骨髓中LAMP1高表达的初治患者一个疗程化疗后不易缓解。骨髓中TPC2高表达的患者一个疗程化疗后更易缓解。
三种膜蛋白的mRNA在AML患者中高表达，LAMP1和TPC1是AML疾病进展的危险因素。TPC2高表达有利于新诊断AML患者的化疗。
