实时荧光定量-PCR检测Notch信号通路相关分子在急性T淋巴细胞白血病中的表达

Expression of Notch signaling pathway related molecules in acute T lymphoblastic leukemia by real-time fluorogentic quantitative PCR

目的:检测Notch信号通路相关分子在急性T淋巴细胞白血病(T cell acute lymphoblastic leukemia,T-ALL)中的表达,并探讨其在T-ALL中的致病机制。方法:采用实时荧光定量-PCR(real-time fluorogentic quantitative PCR,RFQ-PCR)法检测了15例初诊的T-ALL患者的骨髓和11例正常骨髓移植供者细胞中Notch1、Notch2,Notch信号配体分子Jagged1、Delta1,Notch信号途径效应分子Hes1及内参GAPDH的表达水平。结果:T-ALL组患者的骨髓中Notch1的均数表达水平明显高于健康供体组,分别为15105.3±5961.3和1735.5±936.6(P=0.002);Jagged1的表达水平在T-ALL组明显低于健康供体组,分别为231.6±78.4和2192.3±971.6,差异有统计学意义(P=0.000)。Notch2、Delta1和Hes1的表达水平在T-ALL组分别为63067.8±9437.5、368.2±142.5和252.7±94.2,健康供体组为52078.2±8476.3、2189.8±802.3和1006.2±806.0(P值分别为0.452、0.752和0.561),差异无统计学意义;T-ALL组、健康供体组中Notch1和Notch2的表达差异均无统计学意义。结论:Notch1在T-ALL中高表达,而Jagged1在T-ALL则为中低表达,提示T-ALL发病与异常与Notch1信号通路有关;而Notch2与Notch1的表达并不平行。

Objective： To investigate the expression of Notch signaling pathway related molecules in human T cell acute lymphoblastic leukemia（T-ALL） and explore its role in the carcinogenesis of T-ALL . Methods：Real-time fluorogenic quantitative reverse polymerase chain reaction （RFQ-PCR） method was used to detect the expression levels of Notch signaling molecules including Notch1 and Notch2 and Notch signaling ligand molecules Jagged1 and Delta1 and effector molecule Hes1 and internal standard GAPDH in bone marrow of 15 T-ALL patients at the first diagnosis and 11 healthy donors for bone marrow transplantation. Results：The mean expression levels of Notch1 in 15 T-ALL patients were statistically higher than those from 11 healthy donors （15 105.3±5961.3 vs 1 735.5±936.6, P=0.002）; and the mean expression levels of Jagged1 in 15 T-ALL patients were statistically lower than those of 11 donors （231.6± 78.4 vs 2 192.3±971.6, P=0.000）. However, the mean expression levels of Notch2, Delta1, and Hes1 in the 15 T-ALL patients had no significant difference with that in normal healthy donors （63 067.8±9 437.5 vs 52 078.2±8 476.3; 368.2±142.5 vs 2 189.8±802.3; and 252.7±94.2 vs 1 006.2±806.0;P=0.452,0.752,and 0.561,respectively）. There were no statistic differences between Notch1 and Notch 2 expressions in both T-ALL patients and normal healthy donors （P=0.352）. Conclusion： Notch1 was over-expressed in T-ALL while Jagged1 was moderately and weakly expressed in T-ALL, suggesting that abnormal Notch1 signaling pathway was related with leukemogenesis of T-ALL. But the expression of Notch 2 did not parallel with the expression of Notch1.