Balamurugan S, Sugapriya D, Shanthi P, Thilaka V, Venkatadesilalu S, Pushpa V, Madhavan M
Dept of pathology, Madras Medical College, Chennai, 600 002 India.
Indian J Hematol Blood Transfus. 2007 Dec;23(3-4):73-8. doi: 10.1007/s12288-008-0002-2. Epub 2008 Mar 19.
The multidrug resistance 1 (MDR1) gene product, P-glycoprotein (Pgp/p170) is a membrane protein, which acts as an ATP dependant efflux pump that expels a wide variety of organic compounds including chemotherapeutic agents from the cell. Pgp over expression has been demonstrated to be linked with poor treatment outcome and poor prognosis in a number of malignant tumors. AgNORs is a simple, reliable and inexpensive method of evaluating the proliferative activity of a tumor. We have studied MDR1 expression and AgNORS in 41 cases of acute leukemia in children. In this study, AgNOR counts in patients with acute lymphoblastic leukemia (ALL) L2 subtype (FAB classification) were significantly higher as compared to the ALL L1 subtype. Similarly, mean AgNOR count in the acute myeloid Leukemia (AML) M2 subtype was significantly higher as compared to the ALL L1 subtype. However, there was no correlation between AgNOR and treatment outcome or between AgNOR counts and MDR1 expression in any of the subtypes of acute leukemia included in this series. In AML, MDR1 gene expression was found to be related to reduced remission induction rates and hence poorer prognosis. In ALL, our study has shown no difference in remission induction between MDR1 positive and MDR1 negative cases. This would suggest that factors other than MDR1 may be of relevance in Pediatric ALL.
多药耐药 1(MDR1)基因产物 P-糖蛋白(Pgp/p170)是一种膜蛋白,它作为一种依赖 ATP 的外排泵,可将包括化疗药物在内的多种有机化合物排出细胞。Pgp 的过度表达已被证明与多种恶性肿瘤的治疗效果不佳和预后不良有关。核仁组成区嗜银蛋白(AgNORs)是一种评估肿瘤增殖活性的简单、可靠且廉价的方法。我们对 41 例儿童急性白血病患者的 MDR1 表达和 AgNORs 进行了研究。在本研究中,急性淋巴细胞白血病(ALL)L2 亚型(FAB 分类)患者的 AgNOR 计数显著高于 ALL L1 亚型。同样,急性髓系白血病(AML)M2 亚型的平均 AgNOR 计数显著高于 ALL L1 亚型。然而,在本系列纳入的任何急性白血病亚型中,AgNOR 与治疗效果之间或 AgNOR 计数与 MDR1 表达之间均无相关性。在 AML 中,发现 MDR1 基因表达与缓解诱导率降低有关,因此预后较差。在 ALL 中,我们的研究表明 MDR1 阳性和 MDR1 阴性病例在缓解诱导方面没有差异。这表明除 MDR1 之外的其他因素可能与儿童 ALL 有关。