MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.
Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.
1] Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain [2] Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
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Díaz-Beyá
1] Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain [2] 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.
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Brunet
1] Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain [2] Laboratory of Hematology Service, Institut d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Nomdedéu
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
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Tejero
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
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Díaz
1] Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain [2] Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
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Pratcorona
Hematology Department, Hospital Clínico, Valencia, Spain.
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Tormo
Hematology Department, Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Badalona, Spain.
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Ribera
Hematology Department, Hospital Joan XXIII, Tarragona, Spain.
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Escoda
Department of Hematology, Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, Barcelona, Spain.
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Duarte
Hematology Department, Catalan Institute of Oncology (ICO), Girona, Spain.
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Gallardo
Department of Hematology, University Hospital Morales Meseguer, Murcia, Spain.
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Heras
Department of Hematology, Hospital Virgen de la Victoria, Málaga, Spain.
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Queipo de Llano
Department of Hematology, Hospital de Son Llàtzer, Palma de Mallorca, Spain.
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Bargay
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.
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Monzo
1] Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain [2] 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.
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Sierra
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
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Navarro
1] Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain [2] Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
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Esteve
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D000090243:Nucleophosmin; D011379:Prognosis; D012306:Risk
D018398:Homeodomain Proteins; D035683:MicroRNAs; C000716967:NPM1 protein, human; C097899:homeobox protein HOXA9; D000090243:Nucleophosmin