title: 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.
abstract: Mantle 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.
authors.affiliation: Division of Haematology, Department of Cellular Biotechnologies and Haematology, Sapienza University, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Monica
authors.initials: M
authors.lastname: Messina
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Simona
authors.initials: S
authors.lastname: Santangelo
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolaro
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: De Propris
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pescarmona
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pulsoni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martelli
authors.forename: Alice
authors.initials: A
authors.lastname: Di Rocco
authors.forename: Erica
authors.initials: E
authors.lastname: Finolezzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoloni
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Mauro
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002448:Cell Adhesion / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007946:Leukemia, Mast-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness
chemical_list: D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1