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Título
The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature
Autor(es)
Diaz-Beya, Marina | Brunet, Salut | Nomdedeu, Josep | Pratcorona, Marta | Cordeiro, Anna | Gallardo, David | Escoda, Lourdes | Tormo, Mar | Heras, Inmaculada | Maria Ribera, Josep | Duarte, Rafael | Queipo de Llano, Maria Paz | Bargay Lleonart, Joan | Sampol Mayol, Antonia | Nomdedeu, Meritxell | Risueno, Ruth M | Hoyos, Montserrat | Sierra, Jorge | Monzo, Mariano | Navarro, Alfons | Esteve, Jordi | Cooperative AML Grp CETLAM
Fecha de publicación
2015-10-13
Cita
Diaz-Beya M, Brunet S, Nomdedeu J, Pratcorona M, Cordeiro A, Gallardo D, et al. The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature. Oncotarget. 2015 Oct 13;6(31):31613-27.
Idioma
Inglés
Tipo de documento
research article
Resumen
Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown. We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients. The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6; 9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival OR: 2.04; P = 0.001), shorter leukemia-free survival (OR: 2.56; P < 0.001) and a higher cumulative incidence of relapse (OR: 1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33- microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004). Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature.
Palabras clave
MESH
Disease-Free Survival | Disease Progression | Aged | Homeodomain Proteins | Young Adult | Adult | Risk Assessment | Humans | Cytogenetic Analysis | Phenotype | Male | Multivariate Analysis | Predictive Value of Tests | Time Factors | Chi-Square Distribution | MicroRNAs | Biomarkers, Tumor | Female | Risk Factors | Gene Expression Regulation, Neoplastic | Genetic Predisposition to Disease | Kaplan-Meier Estimate | RNA, Long Noncoding | Leukemia, Myeloid, Acute | Adolescent | Middle Aged | Nuclear Proteins | Mutation | Gene Expression Profiling | Proportional Hazards Models | Treatment Outcome | Odds Ratio
DECS
Modelos de Riesgos Proporcionales | Resultado del Tratamiento | Oportunidad Relativa | Análisis Citogenético | Femenino | Proteínas Nucleares | Adolescente | Masculino | Persona de Mediana Edad | Estimación de Kaplan-Meier | Medición de Riesgo | Progresión de la Enfermedad | Proteínas de Homeodominio | Perfilación de la Expresión Génica | Supervivencia sin Enfermedad | Regulación Neoplásica de la Expresión Génica | ARN Largo no Codificante | Distribución de Chi-Cuadrado | Predisposición Genética a la Enfermedad | Factores de Tiempo | Análisis Multivariante | Biomarcadores de Tumor | Mutación | Factores de Riesgo | Humanos | Valor Predictivo de las Pruebas | Adulto Joven | Anciano | Fenotipo | Adulto | Leucemia Mieloide Aguda | MicroARNs
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