PURPOSE: microRNAs (miRNA) are posttranscriptional gene regulators that may be useful as diagnostic and/or prognostic biomarkers. We aim to study the expression profiles of a high number of miRNAs and their relationship with clinicopathologic and biologic relevant features in leukemic mantle cell lymphomas (MCL). EXPERIMENTAL DESIGN: Expression profiling of 664 miRNAs was investigated using a high-throughput quantitative real-time PCR platform in 30 leukemic MCLs. Statistical and bioinformatic analyses were conducted to define miRNAs associated with different clinicopathologic parameters. Gene expression profiling was investigated by microarrays in 16 matching cases to study the potential genes and pathways targeted by selected miRNAs. The prognostic value of miR-34a was investigated in 2 independent series of 29 leukemic and 50 nodal MCLs. RESULTS: Robust consensus clustering defined 2 main MCL subgroups with significant differences in the immunoglobulin (IGHV) mutational status, SOX11 expression, genomic complexity, and nodal clinical presentation. Supervised analyses of IGHV and SOX11 categories identified 17 and 22 miRNAs differentially expressed, respectively. Enriched targets of these miRNAs corresponded to relevant pathways in MCL pathogenesis such as DNA stress response, CD40 signaling, and chromatin modification. In addition, we found 7 miRNAs showing prognostic significance independently of IGHV status and SOX11 expression. Among them, miR-34a was also associated with poor prognosis in 2 independent series of leukemic and nodal MCL, and in cooperation with high expression of the MYC oncogene. CONCLUSION: We have identified miRNAs and target pathways related to clinical and biologic variants of leukemic MCL, and validated miR-34a as a prognostic marker in MCL.
PURPOSE: microRNAs (miRNA) are posttranscriptional gene regulators that may be useful as diagnostic and/or prognostic biomarkers. We aim to study the expression profiles of a high number of miRNAs and their relationship with clinicopathologic and biologic relevant features in leukemic mantle cell lymphomas (MCL). EXPERIMENTAL DESIGN: Expression profiling of 664 miRNAs was investigated using a high-throughput quantitative real-time PCR platform in 30 leukemic MCLs. Statistical and bioinformatic analyses were conducted to define miRNAs associated with different clinicopathologic parameters. Gene expression profiling was investigated by microarrays in 16 matching cases to study the potential genes and pathways targeted by selected miRNAs. The prognostic value of miR-34a was investigated in 2 independent series of 29 leukemic and 50 nodal MCLs. RESULTS: Robust consensus clustering defined 2 main MCL subgroups with significant differences in the immunoglobulin (IGHV) mutational status, SOX11 expression, genomic complexity, and nodal clinical presentation. Supervised analyses of IGHV and SOX11 categories identified 17 and 22 miRNAs differentially expressed, respectively. Enriched targets of these miRNAs corresponded to relevant pathways in MCL pathogenesis such as DNA stress response, CD40 signaling, and chromatin modification. In addition, we found 7 miRNAs showing prognostic significance independently of IGHV status and SOX11 expression. Among them, miR-34a was also associated with poor prognosis in 2 independent series of leukemic and nodal MCL, and in cooperation with high expression of the MYC oncogene. CONCLUSION: We have identified miRNAs and target pathways related to clinical and biologic variants of leukemic MCL, and validated miR-34a as a prognostic marker in MCL.
Authors: L Di Lisio; G Gómez-López; M Sánchez-Beato; C Gómez-Abad; M E Rodríguez; R Villuendas; B I Ferreira; A Carro; D Rico; M Mollejo; M A Martínez; J Menárguez; A Díaz-Alderete; J Gil; J C Cigudosa; D G Pisano; M A Piris; N Martínez Journal: Leukemia Date: 2010-05-20 Impact factor: 11.528
Authors: Verònica Fernàndez; Olga Salamero; Blanca Espinet; Francesc Solé; Cristina Royo; Alba Navarro; Francisca Camacho; Sílvia Beà; Elena Hartmann; Virginia Amador; Luis Hernández; Claudio Agostinelli; Rachel L Sargent; Maria Rozman; Marta Aymerich; Dolors Colomer; Neus Villamor; Steven H Swerdlow; Stefano A Pileri; Francesc Bosch; Miguel A Piris; Emili Montserrat; German Ott; Andreas Rosenwald; Armando López-Guillermo; Pedro Jares; Sergi Serrano; Elías Campo Journal: Cancer Res Date: 2010-02-02 Impact factor: 12.701
Authors: N R Christoffersen; R Shalgi; L B Frankel; E Leucci; M Lees; M Klausen; Y Pilpel; F C Nielsen; M Oren; A H Lund Journal: Cell Death Differ Date: 2009-08-21 Impact factor: 15.828
Authors: Alba Navarro; Sílvia Beà; Verónica Fernández; Miriam Prieto; Itziar Salaverria; Pedro Jares; Elena Hartmann; Anna Mozos; Armando López-Guillermo; Neus Villamor; Dolors Colomer; Xavier Puig; German Ott; Francesc Solé; Sergi Serrano; Andreas Rosenwald; Elías Campo; Luis Hernández Journal: Cancer Res Date: 2009-08-18 Impact factor: 12.701
Authors: Elena Hartmann; Verònica Fernàndez; Victor Moreno; Joan Valls; Luis Hernández; Francesc Bosch; Pau Abrisqueta; Wolfram Klapper; Martin Dreyling; Eva Hoster; Hans Konrad Müller-Hermelink; German Ott; Andreas Rosenwald; Elías Campo Journal: J Clin Oncol Date: 2008-07-07 Impact factor: 44.544