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蒽环类药物与人类白血病中的多药耐药性表达

Anthracycline drugs and MDR expression in human leukemia.

作者信息

Pogliani E M, Belotti D, Rivolta G F, Maffè P F, Corneo G

机构信息

Dept. of Int. Med., University of Milan, S. Gerardo Hospital, Italy.

出版信息

Cytotechnology. 1996;19(3):229-35. doi: 10.1007/BF00744217.

Abstract

We investigated the expression of P-glycoprotein (P-gp) in 50 adults with de novo acute myeloid leukemia (AML) at the initial diagnosis in order to further define the relationship between the presence of P-gp on leukemic cells and the efficacy of two different anthracycline drugs, Daunorubicin (DNR) and Idarubicin (IRR), in terms of remission, induction and survival. We found that 30 (60%) of the 50 patients were negative for P-gp expression (group 1) and 20 patients (40%) were positive (group 2) for P-gp expression by MRK16MoAb using a cut of 10% positive cells. Among the 50 patients, 35 (70%) obtained complete remission (CR); depending on P-gp expression the CR rate was 80% for group 1 and 45% for group 2 (p < 0.005). The median duration of overall survival (OS) was 20 months for patients in group 1, compared to 10 months for patients in group 2 (p < 0.005). Regarding the anthracycline used, no difference in CR has been observed in patients of group 1 (75% CTR with DNR versus 90% CR with IDR); on the contrary in group 2 we observed 40% CR with DNR versus 70% CR with IDR (p < 0.005). No significant difference has been achieved in group 1 terms of median duration of overall survival between DNR and IDR regimen; on the contrary the median duration of OS in patients of group 2 treated with IDR regimen was significantly longer than DNR regimen (p < 0.005). These results confirm the prognostic value of P-gp expression in AML at diagnosis and we suggest that Idarubicin could be a valid anthracycline drug for reversing multidrug resistance.

摘要

我们对50例初诊的成人新发急性髓系白血病(AML)患者中P-糖蛋白(P-gp)的表达进行了研究,以便进一步明确白血病细胞上P-gp的存在与两种不同蒽环类药物柔红霉素(DNR)和伊达比星(IRR)在缓解、诱导和生存方面疗效之间的关系。我们发现,采用MRK16单克隆抗体检测,以10%阳性细胞为界值,50例患者中有30例(60%)P-gp表达为阴性(第1组),20例患者(40%)P-gp表达为阳性(第2组)。在这50例患者中,35例(70%)获得完全缓解(CR);根据P-gp表达情况,第1组的CR率为80%,第2组为45%(p<0.005)。第1组患者的总生存(OS)中位持续时间为20个月,而第2组患者为10个月(p<0.005)。关于所使用的蒽环类药物,第1组患者的CR率未观察到差异(DNR的CR率为75%,IDR为90%);相反,在第2组中,我们观察到DNR的CR率为40%,IDR为70%(p<0.005)。在第1组中,DNR和IDR方案之间的总生存中位持续时间没有显著差异;相反,接受IDR方案治疗的第2组患者的OS中位持续时间明显长于DNR方案(p<0.005)。这些结果证实了诊断时P-gp表达在AML中的预后价值,并且我们认为伊达比星可能是一种有效的用于逆转多药耐药的蒽环类药物。

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