CAJ | 학술논문

[目的] 探讨急性白血病(AL)患者骨髓细胞中间隙连接蛋白43( Cx43)、P-糖蛋白(P-gp)及环氧合酶2(COX-2)基因表达水平及其与AL病程、预后和耐药的关系.[方法] 77例不同病期AL患者,其中初治36例,完全缓解20例,复发20例,同时以20例异体造血干细胞移植供体及非血液系统恶性病患者为对照.采用SYBR Green实时定量反转录聚合酶链反应(SYBR-RT-PCR)技术,检测骨髓单个核细胞中Cx43、P-gp、COX-2mRNA的表达,并对37例初治患者进行动态随访.[结果] AL初治组Cx43、P-gp、COX-2mRNA的表达分别为0.52±0.57、1.42±1.06、1.14±0.95,复发组分别为0.20±0.40、2.29±1.11、1.69±0.81,完全缓解组分别为0.95±0.37、0.93±0.73、0.79±0.58,对照组分别为1.16±0.67、0.86±0.63、0.61 +0.57.初治、复发AL患者Cx43 mRNA表达水平较对照组及完全缓解组低,差异均有统计学意义(初治组分别P=0.001、0.005；复发组均P＜0.001)；完全缓解组Cx43 mRNA表水平与对照组相比,差异无统计学意义( P=0.185).AL患者骨髓细胞液中Cx43 mRNA与P-gp和COX-2mRNA表达呈负相关,且初治组、完全缓解组及复发组表达均呈负相关(与P-gpr值分别为-0.471、-0.362、-0.526;与COX-2 r值分别为-0.479、-0.344、-0.471).36例AL初治患者随访4个月,死亡8例,生存28例,死亡患者Cx43 mRNA表达低于生存患者,差异有统计学意义(t=2.16,P=0.042).[结论] 初治、复发难治AL患者骨髓中Cx43mRNA的表达下调,同时多药耐药基因P-gp、COX-2 mRNA的表达上调；Cx43过度表达是预后良好因素,Cx43与AL的疗效、预后及化疗耐药密切相关.
[목적] 탐토급성백혈병(AL)환자골수세포중간극련접단백43( Cx43)、P-당단백(P-gp)급배양합매2(COX-2)기인표체수평급기여AL병정、예후화내약적관계.[방법] 77례불동병기AL환자,기중초치36례,완전완해20례,복발20례,동시이20례이체조혈간세포이식공체급비혈액계통악성병환자위대조.채용SYBR Green실시정량반전록취합매련반응(SYBR-RT-PCR)기술,검측골수단개핵세포중Cx43、P-gp、COX-2mRNA적표체,병대37례초치환자진행동태수방.[결과] AL초치조Cx43、P-gp、COX-2mRNA적표체분별위0.52±0.57、1.42±1.06、1.14±0.95,복발조분별위0.20±0.40、2.29±1.11、1.69±0.81,완전완해조분별위0.95±0.37、0.93±0.73、0.79±0.58,대조조분별위1.16±0.67、0.86±0.63、0.61 +0.57.초치、복발AL환자Cx43 mRNA표체수평교대조조급완전완해조저,차이균유통계학의의(초치조분별P=0.001、0.005；복발조균P＜0.001)；완전완해조Cx43 mRNA표수평여대조조상비,차이무통계학의의( P=0.185).AL환자골수세포액중Cx43 mRNA여P-gp화COX-2mRNA표체정부상관,차초치조、완전완해조급복발조표체균정부상관(여P-gpr치분별위-0.471、-0.362、-0.526;여COX-2 r치분별위-0.479、-0.344、-0.471).36례AL초치환자수방4개월,사망8례,생존28례,사망환자Cx43 mRNA표체저우생존환자,차이유통계학의의(t=2.16,P=0.042).[결론] 초치、복발난치AL환자골수중Cx43mRNA적표체하조,동시다약내약기인P-gp、COX-2 mRNA적표체상조；Cx43과도표체시예후량호인소,Cx43여AL적료효、예후급화료내약밀절상관.
[Objective] To detect the expression levels of connexin43(Cx43),P-gp and COX-2 in bone marrow of patients with acute leukemia (AL),and investigate their relationship with the pathogenesis,prognosis and resistance of this condition.[Methods]Using SYBR green real-time quantitative reverse transcription polymerase chain reaction (SYBR-RT-PCR),the expression of Cx43,P-gp and COX-2 mRNA were detected in 77 AL patients at different phases,including 36 initially-treated,20 complete-remission (CR)and 20 relapsed.A follow-up was done in those initially lreated.[Results]Expression levels of Cx43,P-gp and COX-2 mRNA from initially-treated were 0.52±0.57,1.42 ±1.06,1.14±0.95;those from relapse AL patients were 0.20±0.40,2.29 ±1.11,1.69±0.81,respectively,those from CR patients were 0.95±0.37,0.93±-0.73,0.79±0.58,respectively,those from normal patients were 1.16 ±0.67,0.86±0.63,0.61±0.57.Expression levels of Cx43 mRNA in initially-treated and relapse AL patients were significantly lower than those in normal patients and CR patients (initially-treated P were 0.001,0.005;relapse patients were P＜0.001),while the comparison between normal patients and CR patients showed no statistical significance (P=0.185).Cx43mRNA expression level was negatively correlated with P-gp and COX-2 mRNA,and a negative correlation was noted of both two expressions in initially-treated and relapse groups (Cx43 mRNA and P-gp mRNA r were -0.471,-0.362,-0.526;Cx43 mRNA and COX-2 mRNA r were -0.479,-0.344,-0.471).A follow-up of four months was conducted in 36 initially-treated patients,eight of them died.The expression Cx43 in those who died was lower than that who survived.The difference was significant(t=2.16,P=0.042).[Conclusion] Cx43mRNA expression levels of initially-treated and relapse AL patients were lower than those in normal patients and CR patients,P-gp and COX-2 mRNA expression levels of initially-treated and relapse AL patients were higher than those in normal patients and CR patients.Cx43 expre-ssion probably is a favorable prognostic factor.Cx43 is participation in the genesis,development and drug resistance of AL.