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

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

doi:10.18632/oncotarget.5148

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

Marina Díaz-Beyá, Salut Brunet, Josep Nomdedéu, Marta Pratcorona, Anna Cordeiro, David Gallardo, Lourdes Escoda, Mar Tormo, Inmaculada Heras, Josep Maria Ribera, Rafael Duarte, María Paz Queipo de Llano, Joan Bargay, Antonia Sampol, Meritxell Nomdedeu, Ruth M. Risueño, Montserrat Hoyos, Jorge Sierra, Mariano Monzo, Alfons NavarroJordi Esteve

Departament de Medicina

Producció científica: Contribució a una revista › Article › Recerca › Avaluat per experts

76 Cites (Scopus)

Resum

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.

Idioma original	English
Pàgines (de-a)	31613-31627
Revista	Oncotarget
Volum	6
Número	31
DOIs	https://doi.org/10.18632/oncotarget.5148
Estat de la publicació	Publicada - 1 de gen. 2015

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10.18632/oncotarget.5148

https://ddd.uab.cat/record/163247

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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., ... Esteve, J. (2015). 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, 6(31), 31613-31627. https://doi.org/10.18632/oncotarget.5148

@article{ce61bf32f10247dea93becbd25c59926,

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.",

keywords = "AML, HOTAIRM, HOX, LncRNA, lincRNA",

author = "Marina D{\'i}az-Bey{\'a} and Salut Brunet and Josep Nomded{\'e}u and Marta Pratcorona and Anna Cordeiro and David Gallardo and Lourdes Escoda and Mar Tormo and Inmaculada Heras and Ribera, {Josep Maria} and Rafael Duarte and {de Llano}, {Mar{\'i}a Paz Queipo} and Joan Bargay and Antonia Sampol and Meritxell Nomdedeu and Risue{\~n}o, {Ruth M.} and Montserrat Hoyos and Jorge Sierra and Mariano Monzo and Alfons Navarro and Jordi Esteve",

year = "2015",

month = jan,

day = "1",

doi = "10.18632/oncotarget.5148",

language = "English",

volume = "6",

pages = "31613--31627",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals",

number = "31",

}

Díaz-Beyá, M, Brunet, S, Nomdedéu, J, Pratcorona, M, Cordeiro, A, Gallardo, D, Escoda, L, Tormo, M, Heras, I, Ribera, JM, Duarte, R, de Llano, MPQ, Bargay, J, Sampol, A, Nomdedeu, M, Risueño, RM, Hoyos, M, Sierra, J, Monzo, M, Navarro, A & Esteve, J 2015, '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, vol. 6, núm. 31, pàg. 31613-31627. https://doi.org/10.18632/oncotarget.5148

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. / Díaz-Beyá, Marina; Brunet, Salut; Nomdedéu, Josep et al.
In: Oncotarget, Vol. 6, Núm. 31, 01.01.2015, pàg. 31613-31627.

Producció científica: Contribució a una revista › Article › Recerca › Avaluat per experts

TY - JOUR

T1 - 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

AU - Díaz-Beyá, Marina

AU - Brunet, Salut

AU - Nomdedéu, Josep

AU - Pratcorona, Marta

AU - Cordeiro, Anna

AU - Gallardo, David

AU - Escoda, Lourdes

AU - Tormo, Mar

AU - Heras, Inmaculada

AU - Ribera, Josep Maria

AU - Duarte, Rafael

AU - de Llano, María Paz Queipo

AU - Bargay, Joan

AU - Sampol, Antonia

AU - Nomdedeu, Meritxell

AU - Risueño, Ruth M.

AU - Hoyos, Montserrat

AU - Sierra, Jorge

AU - Monzo, Mariano

AU - Navarro, Alfons

AU - Esteve, Jordi

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - AML

KW - HOTAIRM

KW - HOX

KW - LncRNA

KW - lincRNA

U2 - 10.18632/oncotarget.5148

DO - 10.18632/oncotarget.5148

M3 - Article

SN - 1949-2553

VL - 6

SP - 31613

EP - 31627

JO - Oncotarget

JF - Oncotarget

IS - 31

ER -

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 gen. 1;6(31):31613-31627. doi: 10.18632/oncotarget.5148