Original Article

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Blood Res 2019; 54(1):

Published online March 31, 2019

https://doi.org/10.5045/br.2019.54.1.57

© The Korean Society of Hematology

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

Ahmed M. L. Bedewy1*, Shereen M. Elmaghraby1, and Noha S. Kandil2

1Hematology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

2Chemical Pathology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Correspondence to : Correspondence to Ahmed M. L. Bedewy, M.D. Hematology Department, Medical Research Institute, Alexandria University, Abraj Al-Shaker from Zaky Ragab Street, Smouha, Alexandria 21615, Egypt. dr_ahmed_bedewy@yahoo.com

Received: July 21, 2018; Revised: September 29, 2018; Accepted: October 22, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 (P=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 (P=0.001). Patients in advanced phases expressed higher levels of BMI1 than those in the chronic phase (P=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.

Keywords ABCB1, BMI1, Chronic myeloid leukemia, Imatinib, TKI resistance, Real-time PCR

Article

Original Article

Blood Res 2019; 54(1): 57-62

Published online March 31, 2019 https://doi.org/10.5045/br.2019.54.1.57

Copyright © The Korean Society of Hematology.

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

Ahmed M. L. Bedewy1*, Shereen M. Elmaghraby1, and Noha S. Kandil2

1Hematology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

2Chemical Pathology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Correspondence to:Correspondence to Ahmed M. L. Bedewy, M.D. Hematology Department, Medical Research Institute, Alexandria University, Abraj Al-Shaker from Zaky Ragab Street, Smouha, Alexandria 21615, Egypt. dr_ahmed_bedewy@yahoo.com

Received: July 21, 2018; Revised: September 29, 2018; Accepted: October 22, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 (P=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 (P=0.001). Patients in advanced phases expressed higher levels of BMI1 than those in the chronic phase (P=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.

Keywords: ABCB1, BMI1, Chronic myeloid leukemia, Imatinib, TKI resistance, Real-time PCR

Fig 1.

Figure 1.

Kaplan-Meier analysis of progression hazard according to ABCB1 expression level (P=0.289).

Blood Research 2019; 54: 57-62https://doi.org/10.5045/br.2019.54.1.57

Fig 2.

Figure 2.

Kaplan-Meier analysis of progression hazard according to BMI1 expression level (P=0.052).

Blood Research 2019; 54: 57-62https://doi.org/10.5045/br.2019.54.1.57
Expression levels of ABCB1 and BMI1 in cases and controls.

a)P-value of Mann-Whitney test. *Significant..


ABCB1 and BMI1 expression in relation to the studied parameters.

a)P-value of student t test. b)P-value of Chi square test. c)P-value of Wilcoxon Signed Rank test. d)P-value of Monte Carlo test. *Significant..


Response to imatinib in relation to ABCB1 and BMI1 expression.

a)P-value of Mann-Whitney test. *Significant..


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