Narjes Mehrvar, Hassan Abolghasemi, Mohammad Reza Rezvany, Mohammad Esmaeil Akbari, Javad Saberynejad, Azim Mehrvar, Mohammad Ali Ehsani, Mahyar Nourian, Ibrahim Qaddoumi, Abolfazl Movafagh,
Volume 8, Issue 2 (Vol.8 No.2 July 2019)
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.
Conclusions: 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.
Mohammad Ali Esmaili, Ahmad Kazemi, Farhad Zaker, Mohammad Faranoush, Mohammad Reza Rezvany,
Volume 8, Issue 4 (Vol.8 No.4 Jan 2020)
Abstract
Background: The current study aims to investigate the relationship of miR-24 expression with plasma methotrexate (MTX) levels, therapy-related toxicities, and event-free survival (EFS) in Iranian pediatric acute lymphoblastic leukemia (ALL) patients.
Methods: The study included 74 ALL patients in consolidation phase and 41 healthy children. RNA was extracted from plasma, polyadenylated, and reverse transcribed. miR-24 expression was determined by quantitative polymerase chain reaction (qPCR). Plasma MTX concentrations were measured by high performance liquid chromatography (HPLC) 48 h after high-dose methotrexate (HD-MTX) injection. The diagnosis of ALL was further subclassified as B-ALL or T-ALL via flow cytometry.
Results: miR-24 expression was less in pediatric ALL patients than in the control group (p = 0.0038). Furthermore, downregulation of miR-24 was correlated with intermediate-to high-grade HD-MTX therapy toxicities (p = 0.025). Nevertheless, no statistically significant associations were seen between miR-24 levels and plasma MTX levels 48 h after HD-MTX administration (p > 0.05) or EFS in pediatric ALL patients (p > 0.05).
Conclusions: miR-24 expression may contribute to interindividual variability in response to intermediate-to high-grade HD-MTX therapy toxicities under Berlin Frankfurt Munster (BFM) treatment.
