Circulating microRNA expression profile in B-cell acute lymphoblastic leukemia

Subtitle:

Article type: Research Article

Authors: Luna-Aguirre, Claudia Maribel^a | de la Luz Martinez-Fierro, Margarita^b | Mar-Aguilar, Fermín^c | Garza-Veloz, Idalia^b | Treviño-Alvarado, Víctor^d | Rojas-Martinez, Augusto^{a; e} | Jaime-Perez, Jose Carlos^f | Malagon-Santiago, Guadalupe Ismael^c | Gutierrez-Aguirre, Cesar Homero^f | Gonzalez-Llano, Oscar^f | Salazar-Riojas, Rosario^f | Hidalgo-Miranda, Alfredo^g | Martinez-Rodriguez, Herminia Guadalupe^a | Gomez-Almaguer, David^f | Ortiz-Lopez, Rocio^{a; e; *}

Affiliations: [a] Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey NL, México | [b] Laboratorio de Medicina Molecular, Unidad Académica de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas, México | [c] Departamento de Biología Celular y Genética, Facultad de Ciencias Biológicas, Monterrey NL, México | [d] Departamento de Ciencias Computacionales, ITESM, Campus Monterrey, Monterrey NL, México | [e] Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, Monterrey, México | [f] Servicio de Hematología, Hospital Universitario Universidad Autónoma de Nuevo León, Monterrey NL, México | [g] Instituto Nacional de Medicina Genómica, México D.F. Periférico Sur, México

Correspondence: [*] Corresponding author: Rocio Ortiz-Lopez, Facultad de Medicina. Universidad Autónoma de Nuevo León, Av. F. I. Madero s.n. Colonia Mitras Centro. Monterrey, Nuevo León, 64349, México. Tel.: +52 81 3404370; Fax: +52 81 83337747; E-mail: [email protected]

Abstract: BACKGROUND: Acute lymphoblastic leukemia (ALL) is a highly diverse disease characterized by cytogenetic and molecular abnormalities, including altered microRNA (miRNA) expression signatures. AIM: We perform and validate a plasma miRNA expression profiling to identify potential miRNA involved in leukemogenesis METHODS: MiRNA expression profiling assay was realized in 39 B-ALL and 7 normal control plasma samples using TaqMan Low Density Array (TLDA) plates on Applied Biosystems 7900 HT Fast Real-Time PCR System. MiRNA validation was done for six miRNA differentially expressed by quantitative real-time PCR. RESULTS: Seventy-seven circulating miRNA differentially expressed: hsa-miR-511, -222, and -34a were overexpressed, whereas hsa-miR-199a-3p, -223, -221, and -26a were underexpressed (p values < 0.005 for both sets). According to operating characteristic curve analysis, hsa-miR-511 was the most valuable biomarker for distinguishing B-ALL from normal controls, with an area under curve value of 1 and 100% for sensitivity, and specificity respectively. CONCLUSIONS: Measuring circulating levels of specific miRNA implicated in regulation of cell differentiation and/or cell proliferation such as hsa-miRNA-511, offers high sensitivity and specificity in B-ALL detection and may be potentially useful for detection of disease progression, as indicator of therapeutic response, and in the assessment of biological and/or therapeutic targets for patients with B-ALL.

Keywords: Biomarkers, hematological malignancies, qRT-PCR, signaling pathway

DOI: 10.3233/CBM-150465

Journal: Cancer Biomarkers, vol. 15, no. 3, pp. 299-310, 2015