TY - JOUR
T1 - Histone deacetylase 1, 2, 6 and acetylated histone H4 in B- and T-cell lymphomas
AU - Marquard, Lena
AU - Poulsen, Christian B.
AU - Gjerdrum, Lise Mette
AU - De Nully Brown, Peter
AU - Christensen, Ib J.
AU - Jensen, Peter B.
AU - Sehested, Maxwell
AU - Johansen, Preben
AU - Ralfkiær, Elisabeth
PY - 2009/5/1
Y1 - 2009/5/1
N2 - Aims: 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. Methods and 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.
AB - Aims: 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. Methods and 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.
KW - Acetylation
KW - Diffuse large B-cell lymphoma
KW - Histone deacetylases
KW - Histone H4
KW - Immunohistochemistry
KW - Peripheral T-cell lymphoma
KW - Survival
KW - Unspecified
UR - http://www.scopus.com/inward/record.url?scp=65349137584&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2559.2009.03290.x
DO - 10.1111/j.1365-2559.2009.03290.x
M3 - Article
C2 - 19438744
AN - SCOPUS:65349137584
VL - 54
SP - 688
EP - 698
JO - Histopathology
JF - Histopathology
SN - 0309-0167
IS - 6
ER -