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.


Autoria(s): Díaz-Beyá, Marina; Brunet, Salut; Nomdedéu, Josep; Pratcorona, Marta; Cordeiro, Anna; Gallardo, David; Escoda, Lourdes; Tormo, Mar; Heras, Inmaculada; Ribera, Josep María; Duarte, Rafael; Queipo de Llano, María Paz; Bargay, Joan; Sampol, Antonia; Nomdedéu, Meritxell; Risueño, Ruth M; Hoyos, Montserrat; Sierra, Jorge; Monzo, Mariano; Navarro, Alfons; Esteve, Jordi
Data(s)

23/11/2015

23/11/2015

13/10/2015

Resumo

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.

Journal Article;

Marina Díaz-Beyá is supported by ISCII (Rio Hortega CM13/00205). This research was in part supported by Fundación Española de Hematologia y Hemoterapia (beca de investigación MDB). This research is also supported by grants from Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III PI13/00999 (IP:Dr. Jordi Esteve), RETICS RD12/0036/0010 (JE;MDB) and SDCSD from School of Medicine, University of Barcelona, AECC-Catalunya 2013 (AN) (sponsored by Mat Holding). Anna Cordeiro is an APIF fellow of the University of Barcelona.

Identificador

Díaz-Beyá M, Brunet S, Nomdedéu 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; 6(31):31613-27

1949-2553 (Online)

http://hdl.handle.net/10668/2065

26436590

10.18632/oncotarget.5148

Idioma(s)

en

Publicador

Impact Journals

Relação

Oncotarget

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=5148&pubmed-linkout=1

Direitos

Acceso abierto

Palavras-Chave #Leucemia mieloide aguda #Leucemia promielocítica aguda #MicroARNs #Pronóstico #ARN no traducido #Recurrencia #Genómica #Humanos #lincRNA #AML #HOTAIRM #HOX #lncRNA #Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute #Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute::Leukemia, Promyelocytic, Acute #Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis #Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated #Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence #Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics #Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/published

Artículo