RESUMEN

BACKGROUND: Relapse remains a critical challenge in children with acute lymphoblastic leukemia (ALL). The emergence of immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs), and T regulatory (Treg) cells, has been considered one potential mechanism of relapse in children with ALL. AIM: This study aimed to address the microRNAs (miRNAs) related to MDSCs and Treg cells and to explore their targeted immunoregulatory pathways. METHODS: Affymetrix microarray was used for global miRNA profiling in B-ALL pediatric patients before, during, and after induction of chemotherapy. Bioinformatics analysis was performed on MDSCs and Treg cells-related dysregulated miRNAs, and miR-Pathway analysis was performed to explore their targeted immunoregulatory pathways. RESULTS: 516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Among them, 13 miRNAs and 8 miRNAs related to MDSCs and Treg cells, respectively, were common in all patients. Besides, 12 miRNAs were shared between MDSCs and Treg cells; 4 of them were common in all patients. Four immune-related pathways; TNF, TGF-ß, FoxO, and Hippo were found implicated. CONCLUSION: Our pilot study concluded certain miRNAs related to MDSCs and Treg cells, these miRNAs were linked to immunoregulatory pathways. Our results open avenues for testing those miRNA as molecular biomarkers for the immunosuppressive tumor microenvironment.

Asunto(s)

Regulación Leucémica de la Expresión Génica/inmunología , MicroARNs/metabolismo , Células Supresoras de Origen Mieloide/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Linfocitos T Reguladores/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Preescolar , Biología Computacional , Femenino , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Voluntarios Sanos , Humanos , Masculino , MicroARNs/sangre , Células Supresoras de Origen Mieloide/efectos de los fármacos , Células Supresoras de Origen Mieloide/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Proyectos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Escape del Tumor/efectos de los fármacos , Escape del Tumor/genética , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología