急性早幼粒细胞白血病维甲酸耐药性的双向电泳分析

目的:研究急性早幼粒细胞白血病(APL)对全反式维甲酸(ATRA)治疗敏感和耐药患者的外周血淋巴细胞在蛋白质组水平上的差异。方法:采用双向凝胶电泳(2-DE)对敏感和耐药患者的外周血淋巴细胞进行蛋白质组差异分析。结果:ATRA敏感和耐药患者外周血淋巴细胞的2-DE平均蛋白质点分别为(746±57)和(617±41),敏感与耐药患者的2-DE相比,有16个蛋白点表达明显上调,22个明显下调。另有4个蛋白点(Mr/pI:24.6kD/8.05,32.3kD/5.17,22.3kD/6.51,25.1kD/7.09)在敏感患者中特异表达,5个蛋白点(Mr/pI:21.9kD/5.45,23.4kD/6.27,22.9kD/6.65,23.9kD/7.39,24.7kD/7.65)在耐药患者中特异表达。结论:结果提示这些差异表达的蛋白质可能与APL对ATRA耐药的机制有关,该研究有助于揭示APL对ATRA耐药机理和发现新的临床分子标志物。

Two- dimensional electrophoresis analysis of mechanism of APL resistant to ATRA

Objective: To explore the differential proteome expressions of lymphocytes in the peripheral blood of the patients with acute promyelocytic leukemia( APL) sensitive to all- trans retinoic acid( ATRA) and the patients with APL resistant to ATRA. Methods: High resolution two- dimensional polyacrylamide gel electrophoresis( 2- DE) was used to analyse lymphocytes in the peripheral blood of the patients with APL sensitive to ATRA and the patients with APL resistant to ATRA. Results: The average protein spots of 2- DE of lymphocytes in the peripheral blood of the patients with APL sensitive to ATRA and the patients with APL resistant to ATRA were 746? 57 and 617? 41, respectively. Compared with the patients resistant to ATRA, the expressions of 16 protein spots increased obviously, in the peripheral blood lymphocytes of the patients with APL sensitive to ATRA, 22, decreased, 4(Mr/ pi: 24. 6kD/ 8. 05, 32. 3kD/ 5. 17, 22. 3kD/ 6. 51, 25. 1kD/ 7. 09) , specifically expressed. 5 protein spots(Mr/ pI: 21. 9kD/ 5. 45, 23. 4kD/ 6. 27, 22. 9kD/ 6. 65, 23. 9kD/ 7. 39, 24. 7kD/ 7. 65) were specifically expressed in the peripheral blood lymphocytes of the patients with APL resistant to ATRA. Conclusion: From the above- mentioned results, it is concluded that these proteins may be involved in the mechanism of ATRA resistance, the differential expression analysis of proteomes may be useful to further study of the ATRA- resistant mechanisms and the molecular markers of APL.