慢性髓性白血病中多药耐药蛋白的表达：关联与意义

Multidrug resistance protein expression in chronic myeloid leukemia: associations and significance.

作者信息

Giles F J, Kantarjian H M, Cortes J, Thomas D A, Talpaz M, Manshouri T, Albitar M

机构信息

Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

出版信息

Cancer. 1999 Sep 1;86(5):805-13.

PMID:10463979

Abstract

BACKGROUND

Overexpression of the multidrug resistance gene (MDR1) product, the MDR1 protein (MDR1), has been associated with poor prognosis in several hematologic malignancies. The significance of MDR1 levels in patients with chronic myeloid leukemia (CML) has not been established.

METHODS

The authors investigated MDR1 levels and their association with patient and tumor characteristics, responsiveness to therapy, and long term prognosis in 198 CML patients. These included 127 patients in early chronic phase (ECP) CML, 31 patients in late chronic phase (LCP) CML, and 40 patients in accelerated or blastic phase CML. MDR1 expression was analyzed by Western blot analysis and quantitative solid-phase plate radioimmunoassay. MDR1 levels were measured on cell lysates obtained from the bone marrow mononuclear cell fraction. Expression was compared in relation to the median derived from 36 normal control samples.

RESULTS

Among patients with CML, high levels of MDR1 were found in 73 of 127 ECP (57%), 20 of 31 LCP (65%), 8 of 27 in accelerated phase (30%), and 8 of 13 in blastic phase (62%) (P value not significant). Furthermore, among the 127 ECP CML patients, high MDR1 levels were associated with age >/=50 years (69% vs. 51%; P < 0. 05), thrombocytosis >700 x 10(9)/L (84% vs. 53%; P < 0.01), and leukocyte counts </=50 x 10(9)/L (70% vs. 46%; P < 0.01). Response to interferon alpha (IFN-alpha) was independent of MDR1 expression; major cytogenetic responses were recorded in 28 of 73 patients with high MDR1 levels and in 16 of 54 patients with low MDR1 levels (38% vs. 30%; P value not significant). No difference in survival based on MDR1 level was observed. A small subset of 17 patients with low MDR1 levels (<1 times normal) had a trend toward worse survival (median, 30 months vs. 73 months; 5-year survival rates of 34% vs. 65%; P = 0.03).

CONCLUSIONS

The results of the current study demonstrate that MDR1 overexpression was not associated with disease progression, responsiveness to IFN-alpha therapy, or survival in patients with ECP CML.

摘要

背景

多药耐药基因（MDR1）产物MDR1蛋白（MDR1）的过表达与多种血液系统恶性肿瘤的不良预后相关。MDR1水平在慢性髓性白血病（CML）患者中的意义尚未明确。

方法

作者调查了198例CML患者的MDR1水平及其与患者和肿瘤特征、治疗反应及长期预后的关系。其中包括127例慢性期早期（ECP）CML患者、31例慢性期晚期（LCP）CML患者以及40例加速期或急变期CML患者。通过蛋白质印迹分析和定量固相板放射免疫测定法分析MDR1表达。在从骨髓单个核细胞组分获得的细胞裂解物上测量MDR1水平。将表达与36个正常对照样品的中位数进行比较。

结果

在CML患者中，127例ECP患者中有73例（57%）、31例LCP患者中有20例（65%）、27例加速期患者中有8例（30%）以及13例急变期患者中有8例（62%）MDR1水平较高（P值无统计学意义）。此外，在127例ECP CML患者中，MDR1高水平与年龄≥50岁（69%对51%；P<0.05）、血小板增多症>700×10⁹/L（84%对53%；P<0.01）以及白细胞计数≤50×10⁹/L（70%对46%；P<0.01）相关。对α干扰素（IFN-α）的反应与MDR1表达无关；73例MDR1水平高的患者中有28例、54例MDR1水平低的患者中有16例记录到主要细胞遗传学反应（38%对30%；P值无统计学意义）。未观察到基于MDR1水平的生存差异。一小部分17例MDR1水平低（<正常1倍）的患者有生存较差的趋势（中位数，30个月对73个月；5年生存率34%对65%；P=0.03）。