Premium
Behind the scenes of non‐nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes
Author(s) -
Del Giudice Ilaria,
Messina Monica,
Chiaretti Sabina,
Santangelo Simona,
Tavolaro Simona,
De Propris Maria Stefania,
Nanni Mauro,
Pescarmona Edoardo,
Mancini Francesca,
Pulsoni Alessandro,
Martelli Maurizio,
Di Rocco Alice,
Finolezzi Erica,
Paoloni Francesca,
Mauro Francesca R.,
Cuneo Antonio,
Guarini Anna,
Foà Robin
Publication year - 2012
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.1365-2141.2011.08962.x
Subject(s) - ighv@ , biology , nodal , mantle cell lymphoma , cancer research , follicular lymphoma , lymphoma , splenic marginal zone lymphoma , chronic lymphocytic leukemia , immunology , genetics , b cell , antibody , leukemia
SummaryMantle cell lymphoma (MCL) is an aggressive neoplasm with a short survival. Cases with leukaemic MCL and splenomegaly without adenopathies (non‐nodal MCL) may have a more indolent course. To gain insights into the biological features underlying this presentation, we investigated the gene expression profile (GEP) and the IGHV mutational status in a cohort of leukaemic MCL cases. Comparison of MCL with other lymphoproliferative disorders (i.e. splenic marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukaemia) revealed a MCL signature enriched for the following gene categories: mitochondrion, oxidoreductase activity, response to stress, to DNA damage and TP53 ‐pathway. Furthermore, GEP analysis revealed that non‐nodal MCL cases were characterized by the down‐modulation of the following gene categories: cell projection, actin cytoskeleton organization, cell adhesion ( ITGAE , CELSR1, PCDH9 ) and tumour invasion/progression ( PGF , ST14 , ETS1 , OCIAD1, EZR ). Many down‐modulated genes were related to the TP53 ‐pathway and to DNA damage response. IGHV status proved unmutated in all nodal and mutated in all non‐nodal MCL. Non‐nodal leukaemic MCLs display a peculiar clinical presentation, with distinctive biological features, such as mutated IGHV and a transcriptional profile lacking tumour invasion properties, that might contribute to the absence of nodal involvement and to the less aggressive clinical course.