ATP-Binding Cassette Transporter Genes and microRNAs in Pediatric B-Cell ALL: Expression Insights

Abstract

Background: Acute lymphocytic leukemia (ALL), characterized by uncontrolled growth of abnormal lymphocytes, predominantly affects children. Genetic analysis focusing on genes and microRNAs reveals important information about the biology of ALL, enabling accurate diagnosis and treatment. This study examines gene and microRNA expression in B cell ALL to improve early diagnosis and personalized treatment.

Methods: Bone marrow samples were collected from patients both before and after the induction phase of chemotherapy. Comprehensive diagnostic techniques including flow cytometry, molecular assays, real-time PCR for common translocations, karyotyping, and complete blood count (CBC) analysis were employed. These methods were utilized to determine the type and risk assessment of ALL, identify specific gene and microRNA expressions, and measure blood cell counts.

Results: The study comprised 12 patients, all under the age of 18. Post-treatment RT-PCR analysis revealed significant reductions in the expression of the ABCB1 gene, miR-129-5p, and miR-9-5p following the induction phase of chemotherapy. Karyotype analysis indicated that two patients were hypodiploid; unfortunately, both of these patients did not survive.

Conclusion: MicroRNAs and ABC genes serve as predictive and prognostic biomarkers in Acute Lymphoblastic Leukemia (ALL) and should be carefully reconsidered. It is more accurate to state that while microRNAs and ABC genes may potentially influence treatment response in ALL, further research is crucial to fully understand their roles in determining treatment outcomes.

Keywords: ABCB1; MicroRNA; acute lymphoblastic leukemia; childhood; relapse.

FIGURE 1

Flow diagram.

FIGURE 2

Strategy gating for ALL analysis by flow cytometry. Sequential gating strategy illustrating the identification and characterization of leukemic cell populations in early pre‐B‐ALL patient sample. Lymphocyte population selection based on FSC and SSC properties. Representative histograms of CD2, CD3, CD5, CD7, CD10, CD13, CD19, CD20, CD33, CD34, TDT and HLA‐DR expression on lymphocytes.

FIGURE 3

(a), (c) The demographic and clinical information of patients including age, sex, type of ALL, karyotype, and molecular abnormality were demonstrated. YO means years old. T means translocation. (+) indicates the presence of an extra chromosome, while (−) indicates the absence of a chromosome. N/A means without abnormality. (b) Kaplan–Meier survival curves of each patient were demonstrated for 36‐month follow‐up. Three patients did not survive during the study.

FIGURE 4

(a) Table displayed CBC information of patients with a mean of each factor. (b) The number of patients based on the normal range of each factor in CBC analysis.

FIGURE 5

RT‐PCR analysis of patients was depicted, showcasing the CT values. Following treatment, a paired t‐test revealed a significant decrease in the expression of the ABCB1 gene, mir‐129‐5q, and mir‐129‐5q.