Histone deacetylase 1, 2, 6 and acetylated histone H4 in B- and T-cell lymphomas.
OBJECTIVE
Histone deacetylase (HDAC) inhibitors are novel therapeutics in the treatment of peripheral T-cell lymphoma, unspecified (PTCL) and diffuse large B-cell lymphoma (DLBCL), where, for unknown reasons, T-cell malignancies appear to be more sensitive than B-cell malignancies. The aim was to determine HDAC expression in DLBCL and PTCL which has not previously been investigated.


RESULTS
The expression of HDAC1, HDAC2, HDAC6 and acetylated histone H4 was examined immunohistochemically in 31 DLBCL and 45 PTCL. All four markers showed high expression in both DLBCL and PTCL compared with normal lymphoid tissue. HDAC1 was more abundantly expressed in PTCL than in DLBCL (P = 0.0046), whereas acetylated H4 was more frequent in DLBCL (P < 0.0001), the latter suggesting a mechanism for T-cell lymphoma sensitivity to HDAC inhibitors. Moderate to strong HDAC6 expression was significantly correlated with favourable outcome (P = 0.016) in DLBCL patients, whereas the opposite effect was observed in PTCL patients (P < 0.0001). The other markers did not correlate with survival (P > 0.05).


CONCLUSIONS
HDAC1, HDAC2, HDAC6 and acetylated H4 are overexpressed in DLBCL and PTCL relative to normal lymphoid tissue. Furthermore, HDAC6 may be an important prognostic marker associated with favourable outcome in DLBCL and a more aggressive course in PTCL.
Department of Pathology, Copenhagen University Hospital, Copenhagen N, Denmark. l.m.ipsen@mail.tele.dk
Lena
L
Marquard
Christian B
CB
Poulsen
Lise Mette
LM
Gjerdrum
Peter
P
de Nully Brown
Ib J
IJ
Christensen
Peter B
PB
Jensen
Maxwell
M
Sehested
Preben
P
Johansen
Elisabeth
E
Ralfkiaer
D000107:Acetylation; D045744:Cell Line, Tumor; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000378:metabolism*
D006657:Histones; D012097:Repressor Proteins; C110550:HDAC1 protein, human; C433811:HDAC6 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases