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
Por:
Díaz-Beyá M., Brunet S., Nomdedéu J., Pratcorona M., Cordeiro A., Gallardo D., Escoda L., Tormo M., Heras I., Ribera J.M., Duarte R., de Llano M.P.Q., Bargay J., Sampol A., Nomdedeu M., Risueño R.M., Hoyos M., Sierra J., Monzo M., Navarro A., Esteve J.
Publicada:
1 ene 2015
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.
Filiaciones:
Díaz-Beyá M.:
Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
Brunet S.:
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
Hematology Service, Institut d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits de Catalunya, Spain
Nomdedéu J.:
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
Laboratory of Hematology Service, Institut d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Pratcorona M.:
Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
Cordeiro A.:
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain
Gallardo D.:
Hematology Department, Catalan Institute of Oncology (ICO), Girona, Spain
Escoda L.:
Hematology Department, Hospital Joan XXIII, Tarragona, Spain
Tormo M.:
Hematology Department, Hospital Clínico, Valencia, Spain
Heras I.:
University Hospital Morales Meseguer, Murcia, Spain
Ribera J.M.:
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
Hematology Department, Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Badalona, Spain
Duarte R.:
Department of Hematology, Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain
de Llano M.P.Q.:
Hospital Virgen de la Victoria, Málaga, Spain
Bargay J.:
Hospital de Son Llàtzer, Palma de Mallorca, Spain
Sampol A.:
Hospital Son Espases, Palma de Mallorca, Spain
Nomdedeu M.:
Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Risueño R.M.:
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
Hoyos M.:
Hematology Service, Institut d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits de Catalunya, Spain
Sierra J.:
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
Hematology Service, Institut d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Banc de Sang i Teixits de Catalunya, Spain
Monzo M.:
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain
Navarro A.:
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain
Esteve J.:
Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain
University of Barcelona, Spain
Gold
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