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00925njm 22002777a 4500 dc Diaz-Beya, Marina author Brunet, Salut author Nomdedeu, Josep author Pratcorona, Marta author Cordeiro, Anna author Gallardo, David author Escoda, Lourdes author Tormo, Mar author Heras, Inmaculada author Maria Ribera, Josep author Duarte, Rafael author Queipo de Llano, Maria Paz author Bargay Lleonart, Joan author Sampol Mayol, Antonia author Nomdedeu, Meritxell author Risueno, Ruth M author Hoyos, Montserrat author Sierra, Jorge author Monzo, Mariano author Navarro, Alfons author Esteve, Jordi author Cooperative AML Grp CETLAM author 2015-10-13 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. 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. 10.18632/oncotarget.5148 1949-2553 Oncotarget http://hdl.handle.net/20.500.13003/10662 26436590 L606687426 2-s2.0-84945568293 http://hdl.handle.net/20.500.12105/20152 363185200101 lincRNA AML HOTAIRM HOX lncRNA 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