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

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.

SUBMITTER: Mehrvar N

PROVIDER: S-EPMC6844611 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Pattern of <i>ABCC</i> Transporter Gene Expression in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia.

Mehrvar Narjes N Abolghasemi Hassan H Rezvany Mohammad Reza MR Esmaeil Akbari Mohammad M Saberynejad Javad J Mehrvar Azim A Ehsani Mohammad Ali MA Nourian Mahyar M Qaddoumi Ibrahim I Movafagh Abolfazl A

Reports of biochemistry & molecular biology 20190701 2

<h4>Background</h4>Abnormal expression of <i>ABCC</i> 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 <i>ABCC1-6</i> and <i>ABCC10</i> genes in Iranian pediatric patients with ALL relapse and determine the potential predictive value of determining ALL relapse from <i>ABCC</i> expression.<h4>Methods</h4>Patients with ALL were divided into two separate groups, ...[more]

PMID: 31832444

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Project description:Relapsed pediatric B-acute lymphoblastic leukemia (B-ALL) remains as the leading cause of cancer death among children. Other than stem cell transplantation and intensified chemotherapy, no other improved treatment strategies have been approved clinically. Gene expression profiling represents a powerful approach to identify potential biomarkers and new therapeutic targets for various diseases including leukemias. However, inadequate sample size in many individual experiments has failed to provide adequate study power to yield translatable findings. With the hope of getting new insights into the biological mechanisms underpinning relapsed ALL and identifying more promising biomarkers or therapeutic targets, we conducted a meta-analysis of gene expression studies involving ALL from 3 separate studies.By using the keywords "acute lymphoblastic leukemia", and "microarray", a total of 280 and 275 microarray datasets were found listed in Gene Expression Omnibus database GEO and ArrayExpress database respectively. Further manual inspection found that only three studies (GSE18497, GSE28460, GSE3910) were focused on gene expression profiling of paired diagnosis-relapsed pediatric B-ALL. These three datasets which comprised of a total of 108 matched diagnosis-relapsed pediatric B-ALL samples were then included for this meta-analysis using RankProd approach.Our analysis identified a total of 1795 upregulated probes which corresponded to 1527 genes (pfp?<?0.01; FC?>?1), and 1493 downregulated probes which corresponded to 1214 genes (pfp?<?0.01; FC?<?1) respectively. S100A8 appeared as the top most overexpressed gene (pfp?<?0.01, FC?=?1.8) and is a potential target for further validation. Based on gene ontology biological process annotation, the upregulated genes were most enriched in cell cycle processes (enrichment score?=?15.3), whilst the downregulated genes were clustered in transcription regulation (enrichment score?=?12.6). Elevated expression of cell cycle regulators (e.g kinesins, AURKA, CDKs) was the key genetic defect implicated in relapsed ALL, and serve as attractive targets for therapeutic intervention.We identified S100A8 as the most overexpressed gene, and the cell cycle pathway as the most promising biomarker and therapeutic target for relapsed childhood B-ALL. The validity of the results warrants further investigation.

Dataset Information

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

Publications

Pattern of <i>ABCC</i> Transporter Gene Expression in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia.

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