title: Biallelic ATM alterations detected at diagnosis identify a subset of treatment-naïve chronic lymphocytic leukemia patients with reduced overall survival similar to patients with p53 deletion.
abstract: The prognostic impact of biallelic ATM abnormalities (ATM mutation and concurrent 11q deletion) remains unknown. We studied ATM, BIRC3, SF3B1, and NOTCH1 genes in 118 treatment-naïve CLL patients at diagnosis. Patients with biallelic ATM alteration had a similar time to first treatment (TTFT) and shorter overall survival (OS) compared with patients with isolated 11q deletion and shorter TTFT and OS when compared to patients with wild-type ATM. Furthermore, biallelic ATM alteration (HR: 6.4; p ≤ 0.007) was significantly associated with an increased risk of death similar to p53 deletion (HR: 6.1; p ≤ 0.004), superior to 11q deletion alone (HR: 2.8; p ≤ 0.022) and independent of other significant parameters such as age, advanced clinical stage, and complex karyotype. Our results suggest the identification of ATM mutations in CLL patients with 11q deletion at diagnosis is clinically relevant and predicts disease progression, poor response to the treatment, and reduced OS independent of other molecular prognostic factors.
authors: a Hematology Department , Molecular Cytogenetics Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.|c Institute of Research Puerta de Hierro-Majadahonda (IDIPHIM) , Spain.
authors: Carol
authors: C
authors: Lozano-Santos
authors: b Hematology Department , Hospital Universitario de Getafe , Madrid , Spain.
authors: José A
authors: JA
authors: García-Vela
authors: a Hematology Department , Molecular Cytogenetics Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors: Nuria
authors: N
authors: Pérez-Sanz
authors: a Hematology Department , Molecular Cytogenetics Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors: Sara
authors: S
authors: Nova-Gurumeta
authors: a Hematology Department , Molecular Cytogenetics Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors: Belen
authors: B
authors: Fernandez-Cuevas
authors: c Institute of Research Puerta de Hierro-Majadahonda (IDIPHIM) , Spain.
authors: Natalia
authors: N
authors: Gomez-Lozano
authors: c Institute of Research Puerta de Hierro-Majadahonda (IDIPHIM) , Spain.
authors: Margarita
authors: M
authors: Sánchez-Beato
authors: d Hematology Departament , Hospital Severo Ochoa de Leganés , Madrid , Spain.
authors: Pedro
authors: P
authors: Sanchez-Godoy
authors: e Blood Bank Unit, Hematology Department , Hospital Universitario Puerta de Hierro-Majadahonda , Madrid , Spain.
authors: José Luis
authors: JL
authors: Bueno
authors: a Hematology Department , Molecular Cytogenetics Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors: José A
authors: JA
authors: Garcia-Marco
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53
chemical_list: D016159:Tumor Suppressor Protein p53; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: 11q deletion; ATM mutation; chronic lymphocytic leukemia; p53 deletion; prognostic markers