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

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

Affiliations
  • 1Hematology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt. dr_ahmed_bedewy@yahoo.com
  • 2Chemical Pathology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

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.

Keyword

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

MeSH Terms

ATP-Binding Cassette Transporters
Disease-Free Survival
Drug Resistance, Multiple
Humans
Imatinib Mesylate*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
RNA, Messenger*
ATP-Binding Cassette Transporters
Imatinib Mesylate
RNA, Messenger

Figure

  • Fig. 1 Kaplan-Meier analysis of progression hazard according to ABCB1 expression level (P=0.289).

  • Fig. 2 Kaplan-Meier analysis of progression hazard according to BMI1 expression level (P=0.052).


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