Copy-number analysis identified new prognostic marker in acute myeloid leukemia.
Recent advances in genomic technologies have revolutionized acute myeloid leukemia (AML) understanding by identifying potential novel actionable genomic alterations. Consequently, current risk stratification at diagnosis not only relies on cytogenetics, but also on the inclusion of several of these abnormalities. Despite this progress, AML remains a heterogeneous and complex malignancy with variable response to current therapy. Although copy-number alterations (CNAs) are accepted prognostic markers in cancers, large-scale genomic studies aiming at identifying specific prognostic CNA-based markers in AML are still lacking. Using 367 AML, we identified four recurrent CNA on chromosomes 11 and 21 that predicted outcome even after adjusting for standard prognostic risk factors and potentially delineated two new subclasses of AML with poor prognosis. ERG amplification, the most frequent CNA, was related to cytarabine resistance, a cornerstone drug of AML therapy. These findings were further validated in The Cancer Genome Atlas data. Our results demonstrate that specific CNA are of independent prognostic relevance, and provide new molecular information into the genomic basis of AML and cytarabine response. Finally, these CNA identified two potential novel risk groups of AML, which when confirmed prospectively, may improve the clinical risk stratification and potentially the AML outcome.
CHU Lille University Hospital, Department of Hematology, Lille, France.
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Nibourel
INSERM UMR-S1172, Institute for Cancer Research of Lille, Factors of Leukemia Cell Persistance, Lille Cedex, France.
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Guihard
CHU Lille University Hospital, Department of Hematology, Lille, France.
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Roumier
CHU Lille University Hospital, Department of Biochemistry and Molecular Biology, Lille, France.
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Pottier
Hospital of Versailles, Department of Hematology, Chesnay, France.
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Terre
University Côte d'Azur, CNRS Institute of Molecular and Cellular Pharmacology, Sophia-Antipolis, Nice, France.
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Paquet
INSERM UMR-S1172, Institute for Cancer Research of Lille, Factors of Leukemia Cell Persistance, Lille Cedex, France.
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Peyrouze
CHU Lille University Hospital, Department of Hematology, Lille, France.
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Geffroy
University Paris Diderot, INSERM U944 Saint-Louis Hospital, Department of Hematology, Paris, France.
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Quentin
University Paris Diderot, INSERM U944 Saint-Louis Hospital, Department of Hematology, Paris, France.
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Alberdi
University Paris Diderot, INSERM U944 Saint-Louis Hospital, Department of Hematology, Paris, France.
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Abdelali
CHU Lille University Hospital, Department of Hematology, Lille, France.
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Renneville
CHU Lille University Hospital, Department of Hematology, Lille, France.
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Demay
University Paris 7, Department of Hematology, Paris, France.
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Celli-Lebras
University Côte d'Azur, CNRS Institute of Molecular and Cellular Pharmacology, Sophia-Antipolis, Nice, France.
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Barbry
INSERM UMR-S1172, Institute for Cancer Research of Lille, Factors of Leukemia Cell Persistance, Lille Cedex, France.
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Quesnel
Hospital of Versailles, Department of Hematology, Chesnay, France.
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Castaigne
University Paris 7, Department of Hematology, Paris, France.
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Dombret
University Paris Diderot, INSERM U944 Saint-Louis Hospital, Department of Hematology, Paris, France.
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Soulier
CHU Lille University Hospital, Department of Hematology, Lille, France.
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Preudhomme
INSERM UMR-S1172, Institute for Cancer Research of Lille, Factors of Leukemia Cell Persistance, Lille Cedex, France.
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Cheok
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D019008:Drug Resistance, Neoplasm; D005260:Female; D018628:Gene Dosage; D016158:Genes, p53; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
D014408:Biomarkers, Tumor