Methylation changes of SIRT1, KLF4, DAPK1 and SPG20 in B-lymphocytes derived from follicular and diffuse large B-cell lymphoma.
Diffuse large-B cell lymphomas (DLBCL) and follicular lymphomas (FL) are the most represented subtypes among mature B-cell neoplasms and originate from malignant B lymphocytes. Methylation represents one of the major epigenetic mechanisms of gene regulation. Silent information regulator 1 (SIRT1) is a class III lysine-deacetylase playing several functions and considered to be a context-dependent tumor promoter. We present the quantitative methylation, gene expression and tissue distribution of SIRT1 and some key mediators related to lymphoma pathogenesis in B lymphocytes purified from biopsies of follicular hyperplasias, FL and DLBCL. SIRT1 mRNA levels are higher in FL than follicular hyperplasias and DLBCL. B cell lymphoma 6 (BCL6) positively correlates with SIRT1. SIRT1 promoter shows a methylation decrease in the order: follicular hyperplasia - FL - DLBCL. Kruppel-like factor 4 (KLF4), Death-associated protein kinase 1 (DAPK1) and Spastic Paraplegia 20 (SPG20) methylation increase significantly in FL and DLBCL compared to follicular hyperplasias. Gene expression of DAPK1 and SPG20 inversely correlates with their degree of methylation. Our findings evidence a positive correlation between SIRT1 and BCL6 expression increase in FL. SIRT1 methylation decreases in FL and DLBCL accordingly and this parallels the increase of KLF4, DAPK1 and SPG20 methylation.
Laboratory of Translational Research, Arcispedale S. Maria Nuova IRCCS, Viale Risorgimento 80, 42124 Reggio Emilia, Italy. Electronic address: raffaele.frazzi@asmn.re.it.
Raffaele
R
Frazzi
Laboratory of Translational Research, Arcispedale S. Maria Nuova IRCCS, Viale Risorgimento 80, 42124 Reggio Emilia, Italy. Electronic address: eleonora.zanetti@asmn.re.it.
Eleonora
E
Zanetti
Laboratory of Translational Research, Arcispedale S. Maria Nuova IRCCS, Viale Risorgimento 80, 42124 Reggio Emilia, Italy. Electronic address: mariaelena.pistoni@asmn.re.it.
Mariaelena
M
Pistoni
Pathology Division, Arcispedale S. Maria Nuova IRCCS, Viale Risorgimento 80, 42124 Reggio Emilia, Italy. Electronic address: ione.tamagnini@asmn.re.it.
Ione
I
Tamagnini
Pathology Division, Arcispedale S. Maria Nuova IRCCS, Viale Risorgimento 80, 42124 Reggio Emilia, Italy. Electronic address: riccardo.valli@asmn.re.it.
Riccardo
R
Valli
Scientific Direction, Arcispedale S. Maria Nuova IRCCS, Viale Umberto I, 42123 Reggio Emilia, Italy. Electronic address: luca.braglia@asmn.re.it.
Luca
L
Braglia
Hematology Division, Arcispedale S. Maria Nuova IRCCS, Viale Risorgimento 80, 42124 Reggio Emilia, Italy. Electronic address: francesco.merli@asmn.re.it.
Francesco
F
Merli
D001402:B-Lymphocytes / Q000378:metabolism*; D018797:Cell Cycle Proteins; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D007150:Immunohistochemistry; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics
D018797:Cell Cycle Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D011506:Proteins; C464787:SPART protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
B lymphocytes; BCL6; Lymphoma; Quantitative methylation; SIRT1