Diaz-Beya, MarinaBrunet, SalutNomdedeu, JosepPratcorona, MartaCordeiro, AnnaGallardo, DavidEscoda, LourdesTormo, MarHeras, InmaculadaMaria Ribera, JosepDuarte, RafaelQueipo de Llano, Maria PazBargay Lleonart, JoanSampol Mayol, AntoniaNomdedeu, MeritxellRisueno, Ruth MHoyos, MontserratSierra, JorgeMonzo, MarianoNavarro, AlfonsEsteve, JordiCooperative AML Grp CETLAM2024-07-042024-07-042015-10-13Diaz-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.http://hdl.handle.net/20.500.13003/10662http://hdl.handle.net/20.500.12105/20152Long 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.enghttps://creativecommons.org/licenses/by/3.0/lincRNAAMLHOTAIRMHOXlncRNADisease-Free SurvivalDisease ProgressionAgedHomeodomain ProteinsYoung AdultAdultRisk AssessmentHumansCytogenetic AnalysisPhenotypeMaleMultivariate AnalysisPredictive Value of TestsTime FactorsChi-Square DistributionMicroRNAsBiomarkers, TumorFemaleRisk FactorsGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseKaplan-Meier EstimateRNA, Long NoncodingLeukemia, Myeloid, AcuteAdolescentMiddle AgedNuclear ProteinsMutationGene Expression ProfilingProportional Hazards ModelsTreatment OutcomeOdds Ratioresearch articleAttribution 3.0 Unported2643659063131613-3162710.18632/oncotarget.51481949-2553Oncotargetopen accessModelos de Riesgos ProporcionalesResultado del TratamientoOportunidad RelativaAnálisis CitogenéticoFemeninoProteínas NuclearesAdolescenteMasculinoPersona de Mediana EdadEstimación de Kaplan-MeierMedición de RiesgoProgresión de la EnfermedadProteínas de HomeodominioPerfilación de la Expresión GénicaSupervivencia sin EnfermedadRegulación Neoplásica de la Expresión GénicaARN Largo no CodificanteDistribución de Chi-CuadradoPredisposición Genética a la EnfermedadFactores de TiempoAnálisis MultivarianteBiomarcadores de TumorMutaciónFactores de RiesgoHumanosValor Predictivo de las PruebasAdulto JovenAncianoFenotipoAdultoLeucemia Mieloide AgudaMicroARNs2-s2.0-84945568293363185200101L606687426