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. 2019 Jul;8(2):184-193.

Pattern of ABCC Transporter Gene Expression in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia

Narjes Mehrvar  1 , Hassan Abolghasemi  2 , Mohammad Reza Rezvany  3   4 , Mohammad Esmaeil Akbari  1 , Javad Saberynejad  5 , Azim Mehrvar  5   6 , Mohammad Ali Ehsani  7 , Mahyar Nourian  6 , Ibrahim Qaddoumi  8 , Abolfazl Movafagh  1   9
Affiliations

Pattern of ABCC Transporter Gene Expression in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia

Narjes Mehrvar et al. Rep Biochem Mol Biol. 2019 Jul.

Abstract

Background: Abnormal expression of ABCC transporter genes has been associated with treatment failure in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate the expression pattern of ABCC1-6 and ABCC10 genes in Iranian pediatric patients with ALL relapse and determine the potential predictive value of determining ALL relapse from ABCC expression.

Methods: Patients with ALL were divided into two separate groups, either the case group with relapsed ALL or the control group in which ALL patients have been in progression-free survival for at least 3 years A total of thirty-nine participants (23 with relapsed ALL; 16 controls) were enrolled over 26 months. To determine the levels of ABCC1-6 and ABCC10 transporter gene expression RT-PCR was used. Cumulative doses of the chemotherapy drugs, VCR, DNR and L-ASP, were calculated for each patient.

Results: Our findings showed elevated expression of ABCC2-6 and decreased expression of ABCC1 and ABCC10 to be associated with an increased risk of ALL relapse. The mean-fold expression of ABCC2 was significantly increased in the ALL relapse group. Additionally, the expression pattern of the ABCC transporter genes was associated with high doses of three chemotherapy drugs, VCR, DNR and L-ASP.

Conclusion: Evaluating the expression pattern of ABCC transporter genes may be a potential biomarker for predicting the occurrence of ALL relapse in Iranian pediatric patients and improve cancer prognosis.

Keywords: ABC transporters; Childhood; Gene expression; Pattern; Recurrence.

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Figures

Fig. 1
Fig. 1
Quantitative real-time PCR analysis with t-test for the mRNAs expression levels of ABCC transporter genes in two groups of relapse and off treatment (3 years progression free survival) patients: A: low expression of ABCC1 in relapse group in comparison to off treatment patients (P-Value: 0.359); B: high expression of ABCC2 in relapse group in comparison to off treatment patients (P-Value: 0.0161); C: high expression of ABCC3 in relapse group in comparison to off treatment patients (P-Value: 0.8042); D: high expression of ABCC4 in relapse group in comparison to off treatment patients (P-Value: 0.1536); E: high expression of ABCC5 in relapse group in comparison to off treatment patients (P-Value: 0.2486); F: high expression of ABCC6 in relapse group in comparison to off treatment patients (P-Value: 0.1046); G: low expression of ABCC10 in relapse group in comparison to off treatment patients (P-Value: 0.9228)
Fig. 2
Fig. 2
ROC curves of ABCC1 and ABCC2 expression for evaluation of sensitivity and specificity in patients: A: high sensitivity between low expression of ABCC1 and occurrence of relapse in considered patients; B: high sensitivity between high expression of ABCC2 and occurrence of relapse in considered patients
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