Haematologica (Mar 2009)

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

  • José Ángel Hernández,
  • Ana Eugenia Rodríguez,
  • Marcos González,
  • Rocío Benito,
  • Celia Fontanillo,
  • Virgilio Sandoval,
  • Mercedes Romero,
  • Guillermo Martín-Núñez,
  • Alfonso García de Coca,
  • Rosa Fisac,
  • Josefina Galende,
  • Isabel Recio,
  • Francisco Ortuño,
  • Juan Luis García,
  • Javier de las Rivas,
  • Norma Carmen Gutiérrez,
  • Jesús F. San Miguel,
  • Jesús María Hernández

DOI
https://doi.org/10.3324/haematol.13862
Journal volume & issue
Vol. 94, no. 3

Abstract

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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.Design and 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 IgVH (p=0.001) and a high level of β2microglobulin (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.