title: 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.
abstract: 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.
authors.affiliation: Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Díaz-Beyá
authors.affiliation: 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.
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.affiliation: 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.
authors.forename: Josep
authors.initials: J
authors.lastname: Nomdedéu
authors.affiliation: Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pratcorona
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cordeiro
authors.affiliation: Hematology Department, Catalan Institute of Oncology (ICO), Girona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Gallardo
authors.affiliation: Hematology Department, Hospital Joan XXIII, Tarragona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escoda
authors.affiliation: Hematology Department, Hospital Clínico, Valencia, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.affiliation: University Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Heras
authors.affiliation: Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.|Hematology Department, Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: Department of Hematology, Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Duarte
authors.affiliation: Hospital Virgen de la Victoria, Málaga, Spain.
authors.forename: María Paz Queipo
authors.initials: MP
authors.lastname: de Llano
authors.affiliation: Hospital de Son Llàtzer, Palma de Mallorca, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Bargay
authors.affiliation: Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Sampol
authors.affiliation: Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Nomdedeu
authors.affiliation: Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Risueño
authors.affiliation: 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.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Hoyos
authors.affiliation: 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.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzo
authors.affiliation: Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.affiliation: 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, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016009:Chi-Square Distribution; D020732:Cytogenetic Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; C000609546:long non-coding RNA HOTAIRM1, human; D000090243:Nucleophosmin; C088144:HoxA protein
keywords: AML; HOTAIRM; HOX; lincRNA; lncRNA