Expression of histone deacetylases in lymphoma: implication for the development of selective inhibitors.
Unselective histone deacetylase (HDAC) inhibitors are a promising novel therapy for lymphoid malignancies. However, these treatments remain empiric as the pattern of HDAC enzymes in different types of cancer, including lymphoid malignancies, remains unknown. We examined the expression of class I and class II HDACs in a panel of cell lines and tissue sections from primary lymphoid tumours. Class I enzymes were highly expressed in all cell lines and primary tumours studied, including the non-malignant reactive cells in the Hodgkin lymphoma (HL) microenvironment. The most frequently altered HDAC expression was HDAC6, as it was either weakly expressed or undetected in 9/14 (64%) of lymphoid cell lines and in 83/89 (93%) of primary lymphoma tissue specimens, including 50/52 (96%) cases of diffuse large B-cell lymphoma, and 18/22 (82%) cases of classical HL. Cell lines that had low expression level of HDAC6 demonstrated aberrant expression of hyper-acetylated tubulin, and were found to be more sensitive to the growth inhibitory effects of the class I HDAC inhibitor MGCD0103. Collectively, our data demonstrate that HDAC6 is rarely expressed in primary lymphoma cases, suggesting that it may not be an important therapeutic target in these lymphoid malignancies.
Gloghini
Annunziata
A
Department of Pathology, National Cancer Institute, Milan, Italy.
Buglio
Daniela
D
Khaskhely
Noor M
NM
Georgakis
Georgios
G
Orlowski
Robert Z
RZ
Neelapu
Sattva S
SS
Carbone
Antonino
A
Younes
Anas
A
D000107:Acetylation; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism* / Q000502:physiology; D006689:Hodgkin Disease / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008198:Lymph Nodes / Q000201:enzymology; D009363:Neoplasm Proteins / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000201:enzymology; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D009363:Neoplasm Proteins; D014404:Tubulin; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases