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Section of Hematology/Oncology and Bone Marrow Transplant, Arizona Cancer Center, University of Arizona College of Medicine, Tuscon 85721, USA.
Leukemia. 1996 Apr;10 Suppl 1:S36-8.
Despite more effective treatment for younger patients with acute myeloid leukemia (AML), resistance to conventional antineoplastics has limited such advances in the elderly. Overexpression of the multidrug transporter, P-glycoprotein (Pgp), appears to contribute to treatment failure in de novo AML and has been detected in up to 70 percent of elderly patients. Data also indicate linkage between Pgp and many adverse prognostic features, including cytogenetic pattern, surface phenotype, and evolution from an antecedent hematologic disorder. Pharmacologic inhibitors of Pgp function have been targeted for investigation in elderly AML patients. Non-Pgp mechanisms responsible for multidrug resistance (MDR) phenotypes that are only weakly sensitive to classic Pgp modulators, however, may limit the success of such strategies. Overexpression of the lung-resistance protein (LRP) in AML has also been linked to advanced age, secondary leukemia, and Pgp overexpression. In a study of 66 patients at the Arizona Cancer Center, LRP overexpression was a more important predictor of response to induction therapy for AML than was Pgp. Recent investigations indicate that overexpression of the gene encoding the MDR-related protein (MRP), though rare in de novo AML, may be common in high-risk groups such as relapsed patients and secondary AML. Use of monoclonal antibodies specific for the MRP gene product may further define its prognostic relevance in AML.
尽管针对年轻急性髓系白血病（AML）患者有了更有效的治疗方法，但老年人对传统抗肿瘤药物的耐药性限制了这些进展。多药转运蛋白P-糖蛋白（Pgp）的过表达似乎导致了初治AML的治疗失败，并且在高达70%的老年患者中被检测到。数据还表明Pgp与许多不良预后特征之间存在联系，包括细胞遗传学模式、表面表型以及由先前血液系统疾病演变而来的情况。Pgp功能的药理抑制剂已成为老年AML患者研究的目标。然而，对经典Pgp调节剂仅具有微弱敏感性的多药耐药（MDR）表型的非Pgp机制，可能会限制此类策略的成功。AML中肺耐药蛋白（LRP）的过表达也与高龄、继发性白血病和Pgp过表达有关。在亚利桑那癌症中心对66例患者的一项研究中，LRP过表达比Pgp更能预测AML诱导治疗的反应。最近的研究表明，编码MDR相关蛋白（MRP）的基因过表达，虽然在初治AML中很少见，但在复发患者和继发性AML等高风险组中可能很常见。使用针对MRP基因产物的单克隆抗体可能会进一步明确其在AML中的预后相关性。
