Genome-wide DNA profiling better defines the prognosis of chronic lymphocytic leukaemia

Andrea Rinaldi, Michael Mian, Ivo Kwee, Davide Rossi, Clara Deambrogi, Afua A. Mensah, Francesco Forconi, Valeria Spina, Emanuele Cencini, Daniela Drandi, Marco Ladetto, Rita Santachiara, Roberto Marasca, Valter Gattei, Franco Cavalli, Emanuele Zucca, Gianluca Gaidano, Francesco Bertoni

Research output: Contribution to journalArticle

Abstract

The integration of molecular and clinical information to tailor treatments remains an important research challenge in chronic lymphocytic leukaemia (CLL). This study aimed to identify genomic lesions associated with a poor outcome and a higher risk of histological transformation. A mono-institutional cohort of 147 cases was used as the test series, and a multi-institutional cohort of 176 cases as a validation series. Genomic profiles were obtained using Affymetrix SNP 6.0. The impact of the recurrent minimal common regions (MCRs) on overall survival was evaluated by univariate analysis followed by multiple-test correction. The independent prognostic significance was assessed by multivariate analysis. Eight MCRs showed a prognostic impact: gains at 2p25.3-p22.3 (MYCN), 2p22.3, 2p16.2-p14 (REL), 8q23.3-q24.3 (MYC), losses at 8p23.1-p21.2, 8p21.2, and of the TP53 locus. Gains at 2p and 8q and TP53 inactivation maintained prognostic significance in multivariate analysis and a hierarchical model confirmed their relevance. Gains at 2p also determined a higher risk of Richter syndrome transformation. The prediction of outcome for CLL patients might be improved by evaluating the presence of gains at 2p and 8q as novel genomic regions besides those included in the 'standard' fluorescence in situ hybridization panel.

Original languageEnglish
Pages (from-to)590-599
Number of pages10
JournalBritish Journal of Haematology
Volume154
Issue number5
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Affymetrix.
  • Leukaemia
  • Prognostic factors
  • Richter's syndrome
  • Transformation

ASJC Scopus subject areas

  • Hematology

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    Rinaldi, A., Mian, M., Kwee, I., Rossi, D., Deambrogi, C., Mensah, A. A., Forconi, F., Spina, V., Cencini, E., Drandi, D., Ladetto, M., Santachiara, R., Marasca, R., Gattei, V., Cavalli, F., Zucca, E., Gaidano, G., & Bertoni, F. (2011). Genome-wide DNA profiling better defines the prognosis of chronic lymphocytic leukaemia. British Journal of Haematology, 154(5), 590-599. https://doi.org/10.1111/j.1365-2141.2011.08789.x