Análisis de la expresión de las isoformas de OCT4 y su significado clínico en leucemias agudas.

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is characterized by the unregulated proliferation of B or T lymphoid precursor cells. Due to their ability to self-renewal, cancer stem cells (CSC) play a crucial role in the origin and progression of ALL. In embryonic and adult stem cells, the expression of the octamer-binding transcription factor 4 (OCT4) is associated with proliferative, pluripotency, and self-renewal characteristics. Alternative splicing generates three isoforms: OCT4A; OCT4B; and OCT4B1. In CSC, carcinogenesis, malignant tumor development, short overall survival, and chemoresistance are promoted by OCT4 expression. Objectives: This study aimed to investigate the expression of the OCT4 isoforms, and the association of isoforms expression and relapse or survival in ALL patients. Material and methods: A total of 80 samples were analyzed: 65 children with ALL; and 15 children without ALL. The immunological phenotype of the blast cells of the cases was evaluated by multiparametric flow cytometry and the analysis of OCT4 isoforms mRNA expression was assessed by RT-qPCR. Results: The expression of OCT4A, OCT4B and OCT4B1 was higher in ALL cases (p-value: 0.0241, 0.0256, 0.0421) than children without ALL. In patients who had relapsed, the OCT4A, OCT4B, and OCT4B1 mRNA expression were increased (p-value: 0.1809, 0.1191, 0.1138). The high expression of OCT4A, OCT4B, and OCT4B1 seem to contribute to the risk of relapse in children with ALL (OR, 2.8, p = 0.097; OR, 2.7, p = 0.106; OR, 1.9, p = 0.283) compared with low expression of OCT4 isoforms and with low-risk clinical characteristics. Conclusion: OCT4 isoforms expressions are elevated in samples from patients with ALL, and especially patients with relapses.