title: A high number of losses in 13q14 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia.
abstract: BACKGROUND
  Among patients with B-cell chronic lymphoid leukemia, those with 13q14 deletion have a favorable outcome. However, whether the percentage of cells with 13q- influences the prognosis or the biological characteristics of this disease is unknown. We analyzed the clinico-biological characteristics and outcome of patients with B-cell chronic lymphoid leukemia with loss of 13q as the sole cytogenetic aberration.
  
  
  METHODS
  Three hundred and fifty patients with B-cell chronic lymphoid leukemia were studied. Clinical data were collected and fluorescence in situ hybridization and molecular studies were carried out. In addition, a gene expression profile was obtained by microarray-based analysis.
  
  
  RESULTS
  In 109 out of the 350 cases (31.1%) loss of 13q was the sole cytogenetic aberration at diagnosis. In the subgroup of patients with 80% or more of cells with loss of 13q (18 cases), the overall survival was 56 months compared with not reached in the 91 cases in whom less than 80% of cells had loss of 13q (p< 0.0001). The variables included in the multivariate analysis for overall survival were the percentage of losses of 13q14 (p=0.001) and B symptoms (p=0.007). The time to first therapy in the group with 80% or more vs. less than 80% of losses was 38 months vs. 87 months, respectively (p=0.05). In the multivariate analysis the variables selected were unmutated status of IgV(H) (p=0.001) and a high level of beta(2)microglobulin (p=0.003). Interestingly, these differences regarding overall survival and time to first therapy were also present when other cut-offs were considered. The gene expression profile of patients with a high number of losses in 13q14 showed a high proliferation rate, downregulation of apoptosis-related genes, and dysregulation of genes related to mitochondrial functions.
  
  
  CONCLUSIONS
  Patients with B-cell chronic lymphoid leukemia with a high number of losses in 13q14 as the sole cytogenetic aberration at diagnosis display different clinical and biological features: short overall survival and time to first therapy as well as more proliferation and less apoptosis. A quantification of the number of cells showing a genetic abnormality should, therefore, be included in the study of the prognostic factors of B-cell chronic lymphoid leukemia.
authors.affiliation: Servicios de Hematología, Hospital Infanta Leonor, Madrid, Spain.
authors.forename: José Angel
authors.initials: JA
authors.lastname: Hernández
authors.forename: Ana Eugenia
authors.initials: AE
authors.lastname: Rodríguez
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Rocío
authors.initials: R
authors.lastname: Benito
authors.forename: Celia
authors.initials: C
authors.lastname: Fontanillo
authors.forename: Virgilio
authors.initials: V
authors.lastname: Sandoval
authors.forename: Mercedes
authors.initials: M
authors.lastname: Romero
authors.forename: Guillermo
authors.initials: G
authors.lastname: Martín-Núñez
authors.forename: Alfonso García
authors.initials: AG
authors.lastname: de Coca
authors.forename: Rosa
authors.initials: R
authors.lastname: Fisac
authors.forename: Josefina
authors.initials: J
authors.lastname: Galende
authors.forename: Isabel
authors.initials: I
authors.lastname: Recio
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortuño
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: García
authors.forename: Javier
authors.initials: J
authors.lastname: de las Rivas
authors.forename: Norma Carmen
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Jesús María
authors.initials: JM
authors.lastname: Hernández
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis