title: Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols.
abstract: BACKGROUND
  Some copy number alterations (CNAs) have independent prognostic significance for adults with acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  This study analyzed via multiplex ligation-dependent probe amplification the frequency and prognostic impact of CNAs of 12 genetic regions in 142 adolescents and adults with de novo precursor B-cell ALL.
  
  
  RESULTS
  The cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion (59 of 142 or 42%) was the most frequent CNA, and it was followed by Ikaros family zinc finger 1 (IKZF1) losses (49 of 142 or 35%). IKZF1 deletions were more prevalent in Philadelphia chromosome (Ph)-positive ALL and were associated with advanced age and high white blood cell (WBC) counts. The multivariate analysis showed that advanced age and early B-cell factor 1 (EBF1) deletions were associated with chemotherapy resistance in both the whole series (hazard ratios, 0.949 and 0.135, respectively) and the Ph-negative subgroup (hazard ratios, 0.946 and 0.118, respectively). High WBC counts and focal IKZF1 deletions correlated with disease recurrence (hazard ratios, 1.005 and 1.869, respectively), whereas advanced age and CDKN2A/B losses influenced overall survival in both the whole series (hazard ratios, 1.038 and 2.545, respectively) and the Ph-negative subgroup (hazard ratios, 1.044 and 2.105, respectively).
  
  
  CONCLUSIONS
  Deletions of EBF1, IKZF1, and CDKN2A/B have an independent adverse prognosis for adolescents and adults with B-precursor ALL, and this suggests that these CNAs should be included in the initial risk assessment of ALL.
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ribera
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Morgades
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Zamora
authors.affiliation: Hematology Department, La Fe Hospital, Valencia, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.affiliation: Hematology Department, La Fe Hospital, Valencia, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Gómez-Seguí
authors.affiliation: Hematology Department, Hospital Clinic, August Pi i Sunyer Institute for Biomedical Research, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pratcorona
authors.affiliation: Hematology Department, Catalan Institute of Oncology at Duran i Reynals Hospital, Hospitalet de Llobregat, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Sarrà
authors.affiliation: Hematology Department, Catalan Institute of Oncology at Josep Trueta Hospital, Girona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Guàrdia
authors.affiliation: Hematology Department, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Nomdedeu
authors.affiliation: Hematology Department, Hospital Clínico, Valencia, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.affiliation: Hematology Department, Doce de Octubre Hospital, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martínez-Lopez
authors.affiliation: Hematology Department, Institute of Biomedical Investigation of Salamanca, Institute of Molecular and Cellular Biology of Cancer, Center of Investigation of Cancer, Spanish National Research Council at University of Salamanca, Hospital Clínico Universitario, Salamanca, Spain.
authors.forename: Jesús-María
authors.initials: JM
authors.lastname: Hernández-Rivas
authors.affiliation: Hematology Department, Vírgen del Rocío Hospital, Seville, Spain.
authors.forename: José
authors.initials: J
authors.lastname: González-Campos
authors.affiliation: Hematology Department, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Barba
authors.affiliation: Hematology Department, Joan XXIII University Hospital, Tarragona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escoda
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Genescà
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Fuensanta
authors.initials: F
authors.lastname: Millá
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Evarist
authors.initials: E
authors.lastname: Feliu
authors.affiliation: Clinical Hematology Department, Catalan Institute of Oncology at Germans Trias i Pujol Hospital, Jose Carreras Leukemia Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Josep-Maria
authors.initials: JM
authors.lastname: Ribera
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D013030:Spain; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; C081976:EBF1 protein, human; C497239:IKZF1 protein, human; D015534:Trans-Activators; D051740:Ikaros Transcription Factor
keywords: B precursor; acute lymphoblastic leukemia; adult; copy number alterations; prognosis