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Genomic and expression profiling identifies the B‐cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma
Author(s) -
Rinaldi Andrea,
Kwee Ivo,
Taborelli Monica,
Largo Cristina,
Uccella Silvia,
Martin Vittoria,
Poretti Giulia,
Gaidano Gianluca,
Calabrese Giuseppe,
Martinelli Giovanni,
Baldini Luca,
Pruneri Giancarlo,
Capella Carlo,
Zucca Emanuele,
Cotter Finbarr E.,
Cigudosa Juan C.,
Catapano Carlo V.,
Tibiletti Maria G.,
Bertoni Francesco
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05883.x
Subject(s) - syk , cancer research , biology , gene expression profiling , mantle cell lymphoma , microbiology and biotechnology , cell , dna microarray , cell growth , tyrosine kinase , gene , gene expression , lymphoma , signal transduction , genetics , immunology
Summary Among B‐cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC . Among the transcripts with high correlation between DNA and RNA, we identified SYK , a tyrosine kinase involved in B‐cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo‐1 cell line. Low‐level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.