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

被引：95

作者：

Diaz-Beya, Marina ^{[1
,2
]}

Brunet, Salut ^{[2
,3
]}

Nomdedeu, Josep ^{[2
,4
]}

Pratcorona, Marta ^{[1
,2
]}

Cordeiro, Anna ^{[5
]}

Gallardo, David ^{[6
]}

Escoda, Lourdes ^{[7
]}

Tormo, Mar ^{[8
]}

Heras, Inmaculada ^{[9
]}

Maria Ribera, Josep ^{[2
,10
]}

Duarte, Rafael ^{[11
]}

Queipo de Llano, Maria Paz ^{[12
]}

Bargay, Joan ^{[13
]}

Sampol, Antonia ^{[14
]}

Nomdedeu, Meritxell ^{[1
]}

Risueno, Ruth M. ^{[2
]}

Hoyos, Montserrat ^{[3
]}

Sierra, Jorge ^{[2
,3
]}

Monzo, Mariano ^{[5
]}

Navarro, Alfons ^{[5
]}

Esteve, Jordi ^{[1
,2
,15
]}

机构：

[1] Hosp Clin Barcelona, Dept Hematol, Inst Invest Bomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

[2] Josep Carreras Leukemia Res Inst IJC, Barcelona, Spain

[3] Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Hosp Santa Creu & St Pau, Hematol Serv, Banc Sang Teixits Catalu, Spain

[4] Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Hosp Santa Creu & St Pau, Lab Hematol Serv, E-08193 Barcelona, Spain

[5] Univ Barcelona, Sch Med, Mol Oncol & Embryol Lab, Human Anat Unit,IDIBAPS, Barcelona, Spain

[6] Catalan Inst Oncol ICO, Hematol Dept, Girona, Spain

[7] Hosp Joan 23, Dept Hematol, Tarragona, Spain

[8] Hosp Clin, Dept Hematol, Valencia, Spain

[9] Univ Hosp Morales Meseguer, Murcia, Spain

[10] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol ICO, Hematol Dept, Badalona, Spain

[11] Hosp Duran & Reynals, Catalan Inst Oncol ICO, Dept Hematol, Barcelona, Spain

[12] Hosp Virgen de la Victoria, Malaga, Spain

[13] Hosp Son Llatzer, Palma De Mallorca, Spain

[14] Hosp Son Espases, Palma De Mallorca, Spain

[15] Univ Barcelona, E-08007 Barcelona, Spain

来源：

ONCOTARGET | 2015年 / 6卷 / 31期

关键词：

lincRNA; AML; HOTAIRM; HOX; lncRNA; GENE-EXPRESSION; HEMATOPOIETIC-CELLS; NONCODING RNAS; NPM1; MUTATIONS; COMPETING RISK; UP-REGULATION; GROUP-B; CANCER; CHROMATIN; PATTERN;

D O I：

10.18632/oncotarget.5148

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：31613 / 31627

页数：15

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