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慢性髓性白血病患者中ABCB1和BMI1 mRNA表达:对伊马替尼疗效的影响

ABCB1 and BMI1 mRNA expression in patients with chronic myeloid leukemia: impact on imatinib efficacy.

作者信息

Bedewy Ahmed M L, Elmaghraby Shereen M, Kandil Noha S

机构信息

Hematology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Chemical Pathology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

出版信息

Blood Res. 2019 Mar;54(1):57-62. doi: 10.5045/br.2019.54.1.57. Epub 2019 Mar 21.

Abstract

BACKGROUND

ATP-binding cassette transporters are important in the mechanism of multidrug resistance. ABCB1 displays a high affinity for imatinib. BMI1 is a polycomb group protein thought to be overexpressed in leukemic cells.

METHODS

This study was conducted to investigate the prognostic value of ABCB1 and BMI1 expressions in chronic myeloid leukemia (CML). Expression levels were measured in 81 patients newly diagnosed with CML and 20 healthy controls by real time reverse transcription- PCR.

RESULTS

The ABCB1 expression levels did not differ between patients with CML and controls. Low ABCB1 mRNA levels were observed in patients who achieved an optimal response compared to suboptimal and resistant cases (=0.005). Non-responders showed the highest ABCB1 levels. ABCB1 expression did not affect the progression-free survival (PFS) of patients. BMI1 expression was higher in patients than that in controls (=0.001). Patients in advanced phases expressed higher levels of BMI1 than those in the chronic phase (=0.004). High BMI1 expression was associated with a shorter PFS.

CONCLUSION

ABCB1 mRNA expression may serve as a predictor of the optimal response to imatinib treatment in patients with CML. BMI1 expression was higher in the accelerated and blastic crisis phases of CML and associated with a shorter PFS.

摘要

背景

ATP结合盒转运蛋白在多药耐药机制中起重要作用。ABCB1对伊马替尼具有高亲和力。BMI1是一种多梳蛋白家族蛋白,被认为在白血病细胞中过表达。

方法

本研究旨在探讨ABCB1和BMI1表达在慢性粒细胞白血病(CML)中的预后价值。通过实时逆转录PCR检测81例新诊断的CML患者和20例健康对照的表达水平。

结果

CML患者和对照之间ABCB1表达水平无差异。与未达到最佳反应和耐药的病例相比,达到最佳反应的患者中观察到低ABCB1 mRNA水平(P=0.005)。无反应者显示出最高的ABCB1水平。ABCB1表达不影响患者的无进展生存期(PFS)。患者的BMI1表达高于对照(P=0.001)。晚期患者的BMI1表达水平高于慢性期患者(P=0.004)。高BMI1表达与较短的PFS相关。

结论

ABCB1 mRNA表达可作为CML患者对伊马替尼治疗最佳反应的预测指标。BMI1表达在CML的加速期和急变期较高,并与较短的PFS相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41e1/6439291/2c395a3b321c/br-54-57-g001.jpg

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