title: Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations.
abstract: Acute myeloid leukemia (AML) with t(8;21) (q22;q22) is considered to have favorable risk; however, nearly half of t(8;21) patients are not cured, and recent studies have highlighted remarkable genetic heterogeneity in this subset of AML. Here we identify somatic mutations in additional sex combs-like 2 (ASXL2) in 22.7% (25/110) of patients with t(8;21), but not in patients with inv(16)/t(16;16) (0/60) or RUNX1-mutated AML (0/26). ASXL2 mutations were similarly frequent in adults and children t(8;21) and were mutually exclusive with ASXL1 mutations. Although overall survival was similar between ASXL1 and ASXL2 mutant t(8;21) AML patients and their wild-type counterparts, patients with ASXL1 or ASXL2 mutations had a cumulative incidence of relapse of 54.6% and 36.0%, respectively, compared with 25% in ASXL1/2 wild-type counterparts (P = .226). These results identify a high-frequency mutation in t(8;21) AML and identify the need for future studies to investigate the clinical and biological relevance of ASXL2 mutations in this unique subset of AML.
authors: Hematology Department, INSERM Unité Mixte de Recherche 1009, Gustave Roussy Cancer Campus Grand Paris, Villejuif, Paris-Sud University, Orsay, France; Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY;
authors: Jean-Baptiste
authors: JB
authors: Micol
authors: Laboratory of Hematology and Tumor Bank, INSERM U837 Team 3, Cancer Research Institute of Lille, Centre Hospitalier Régional Universitaire of Lille, University Lille Nord de France, Lille, France;
authors: Nicolas
authors: N
authors: Duployez
authors: Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique-Hôpitaux de Paris), University Paris Diderot, Paris, France;
authors: Nicolas
authors: N
authors: Boissel
authors: Department of Pediatric Hematology, Hôpital Armand Trousseau (Assistance Publique-Hôpitaux de Paris), Paris, France;
authors: Arnaud
authors: A
authors: Petit
authors: Laboratory of Hematology and Tumor Bank, INSERM U837 Team 3, Cancer Research Institute of Lille, Centre Hospitalier Régional Universitaire of Lille, University Lille Nord de France, Lille, France;
authors: Sandrine
authors: S
authors: Geffroy
authors: Laboratory of Hematology and Tumor Bank, INSERM U837 Team 3, Cancer Research Institute of Lille, Centre Hospitalier Régional Universitaire of Lille, University Lille Nord de France, Lille, France;
authors: Olivier
authors: O
authors: Nibourel
authors: Laboratory of Hematology and Tumor Bank, Hôpital Cochin (Assistance Publique-Hôpitaux de Paris), Paris, France;
authors: Catherine
authors: C
authors: Lacombe
authors: Laboratory of Hematology, Hôpital Armand Trousseau (Assistance Publique-Hôpitaux de Paris), Groupe Hospitalier Universitaire de l'Est Parisien, Paris, France;
authors: Helene
authors: H
authors: Lapillonne
authors: Laboratory of Hematology and Tumor Bank, INSERM U837 Team 3, Cancer Research Institute of Lille, Centre Hospitalier Régional Universitaire of Lille, University Lille Nord de France, Lille, France;
authors: Pascaline
authors: P
authors: Etancelin
authors: Functional and Structural Genomic Platform, Lille 2 University, IFR-114, Lille, France;
authors: Martin
authors: M
authors: Figeac
authors: Laboratory of Hematology and Tumor Bank, INSERM U837 Team 3, Cancer Research Institute of Lille, Centre Hospitalier Régional Universitaire of Lille, University Lille Nord de France, Lille, France;
authors: Aline
authors: A
authors: Renneville
authors: Department of Hematology, Versailles Hospital, Le Chesnay, France;
authors: Sylvie
authors: S
authors: Castaigne
authors: Department of Pediatric Hematology, Hôpital Armand Trousseau (Assistance Publique-Hôpitaux de Paris), Paris, France;
authors: Guy
authors: G
authors: Leverger
authors: Department of Hematology, INSERM U892, Centre Hospitalier Universitaire d'Angers, Angers, France; and.
authors: Norbert
authors: N
authors: Ifrah
authors: Department of Hematology and EA3518, Hôpital Saint-Louis (Assistance Publique-Hôpitaux de Paris), University Paris Diderot, Paris, France;
authors: Hervé
authors: H
authors: Dombret
authors: Laboratory of Hematology and Tumor Bank, INSERM U837 Team 3, Cancer Research Institute of Lille, Centre Hospitalier Régional Universitaire of Lille, University Lille Nord de France, Lille, France;
authors: Claude
authors: C
authors: Preudhomme
authors: Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY;
authors: Omar
authors: O
authors: Abdel-Wahab
authors: Department of Hematology and Oncology, Centre Hospitalier Universitaire de Nimes, University Montpellier-Nimes, Nimes, France.
authors: Eric
authors: E
authors: Jourdan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D012097:Repressor Proteins / Q000235:genetics*; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; C473949:ASXL1 protein, human; C484295:ASXL2 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D012097:Repressor Proteins