急性白血病患者肺耐药蛋白基因表达及其临床意义

The clinical significance of lung resistance protein(LRP) gene expression in patients with acute leukemia

目的 探讨急性白血病 (AL)患者肺耐药蛋白 (LRP)基因表达与临床耐药的关系。方法 应用半定量逆转录 聚合酶链反应 (RT PCR) ,并以 β2 微球蛋白 (β2 MG)作内对照 ,检测了 6 1例AL患者及 15名正常对照者LRP基因的表达 ,将LRP/ β2 MG≥ 0 .3定为LRP阳性。结果 初治组LRP的阳性率为 32 .4% ,LRP阳性与LRP阴性患者的首次完全缓解 (CR1)率分别为 33.3%和 84.0 % ,两者的差异有显著性 (P <0 .0 0 5 ) ;复发难治组LRP基因表达水平及阳性率均显著高于初治组 (P <0 .0 1) ;正常对照组及长期生存组LRP基因表达水平较低 ;LRP基因表达与FAB分型有关。同时检测了 6 1例AL患者多药耐药基因mdr 1的表达 ,发现两种基因同时表达的AL患者预后极差 ;LRP和mdr 1表达之间无相关性 (P >0 .5 )。结论 LRP基因过度表达可导致临床耐药 ,是AL患者预后的重要不利因素。

Objective To investigate the relationship between the expression of lung resistance protein(LRP)gene and drug resistance in patients with acute leukemias(AL). Methods Semi quantitative reverse transcriptase polymerase chain reaction(RT PCR)was used to examine the expression of LRP gene in AL patients and 15 normal subjects. β 2 microglobin (β 2MG) was used as internal reference. LRP/β 2MG ratio≥0.3 was defined as LRP positive. Results The positivity percentage of LRP gene expression in newly diagnosed group was 32.4%. The first complete remission rate was 84.0% and 33.0% in LRP negative and LRP positive patients, respectively.The difference was significant(P<0.005). The expression level of LRP mRNA and the positivity percentage of LRP in relapsed/refractory group were significantly higher than that in newly diagnosed group (P<0.01). The expression level of LRP gene in normal subjects and long term survival groups was very low and correlated with FAB subtypes. The mdr 1 gene was examined simultaneously in 61 AL patients. No significant correlation was found between the expression of LRP and mdr 1 gene (P>0.5). Coexpression of LRP and mdr 1 genes in the same AL patient might result in the worst prognosis. Conclusion High expression of LRP gene leads to clinical drug resistance and is an unfavorable factor to AL patients of prognosis.