Characterizing Iranian Pediatric Patients With Relapsed Acute Lymphoblastic Leukemia Through Gene Expression Profiling of Common ATP Binding Cassette Transporters Subfamily C

Abstract

Background: The correlation between gene expression of ABCC transporters and recurrence as a treatment failure in pediatric patients with acute lymphoblastic leukemia (ALL) is an unsolved problem in scientific associations. The aim of this study was to evaluate the predictive value of ABCC1-6 gene expression pattern for estimating recurrence in Iranian pediatric patients with ALL. Materials and Methods: Iranian pediatric patients with approved ALL enrolled in this study as 2 groups of case (relapsed ALL) and control (treated individuals who lasted for >3 years following their final treatment). Real-time polymerase chain reaction was done with GAPDH for expressing ABCC1-6 transporter genes. Cumulative doses of Vincristine, Daunorubicin, and L-Asparginase were checked for each patient. Gathered data analyzed with SPSS version 22 and REST 2009 software. Results: Thirty-nine samples as 23 relapsed ALL and 16 controls enrolled. High expression of ABCC2-6 and low expression of ABCC1 were detected in pediatric patients with relapse. ABCC3 and ABCC4 had significant relation with high-risk patients of NCI group. Also, ABCC4 and ABCC6 had more expression with high doses of Daunorubicin and L-Asparginase. Conclusions: Designed expression pattern have the predictive value for estimating of conferring relapse in Iranian pediatric patients with diagnosed ALL. The authors suggest of designing a multiple childhood malignancy center project to evaluate this pattern in a cohort study.

Temporal trend and spatial distribution of acute lymphoblastic leukemia in Iranian children during 2006 -2014: A Mixed Ecological Study

“…In the present study, 57.9% (2182 patients) of the disease were observed in boys and the sex ratio of males to females was 1.37. These results are consistent with other studies; other studies showed higher incidence of disease in boys than in girls [4,9,[24][25][26]. According to the American Cancer Society's 2019 report, 55 percent of new cases and 56 percent of ALL deaths were boys [27].…”

Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response

“…An increased expression of ABCC 2 to six was observed in relapsed pediatric ALL patients compared to non-relapsed patients, who also showed a decreased expression of ABCC1. It is also interesting to note that ABCC 4 and 6 was higher among those who received high doses of daunorubicin and L-asparaginase [60].…”

“…In a study of Iranian pediatric ALL patients, a high expression of ABCC2-6 and low expression of ABCC1 were detected in patients with relapse. ABCC4 and ABCC6 expression increased with high doses of daunorubicin and L-asparaginase [60]. Daunorubicin is one of the substrates of OATP1B1 (SLCO1B1).…”

The Battlefield of Chemotherapy in Pediatric Cancers

“…After chemotherapy, MRP1 expression has been observed to be upregulated in neuroblastoma, hepatoblastoma, and rhabdomyosarcoma patients [ 110 ]. Increased expression of MRP2-6 and decreased expression of MRP1 and MRP10 have been observed in ALL patients, which are associated with high doses of three chemotherapies [ 115 ]. Henderson et al found that the inhibition of MPR1 is associated with reduced neuroblastoma development in transgenic mice [ 116 ].…”