Expression of histone deacetylases in lymphoma

Implication for the development of selective inhibitors

Annunziata Gloghini, Daniela Buglio, Noor M. Khaskhely, Georgios Georgakis, Robert Z. Orlowski, Sattva S. Neelapu, Antonino Carbone, Anas Younes

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)515-525
Number of pages11
JournalBritish Journal of Haematology
Volume147
Issue number4
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Histone Deacetylases
Lymphoma
Histone Deacetylase Inhibitors
Neoplasms
Hodgkin Disease
Cell Line
Lymphoma, Large B-Cell, Diffuse
Enzymes
Tubulin
Tumor Cell Line
Lymphocytes
Therapeutics
Growth

Keywords

  • Gene expression profile
  • HDAC
  • HDAC inhibitors
  • Hodgkin lymphoma
  • Reed Sternberg cells

ASJC Scopus subject areas

  • Hematology

Cite this

Expression of histone deacetylases in lymphoma : Implication for the development of selective inhibitors. / Gloghini, Annunziata; Buglio, Daniela; Khaskhely, Noor M.; Georgakis, Georgios; Orlowski, Robert Z.; Neelapu, Sattva S.; Carbone, Antonino; Younes, Anas.

In: British Journal of Haematology, Vol. 147, No. 4, 11.2009, p. 515-525.

Research output: Contribution to journalArticle

Gloghini, A, Buglio, D, Khaskhely, NM, Georgakis, G, Orlowski, RZ, Neelapu, SS, Carbone, A & Younes, A 2009, 'Expression of histone deacetylases in lymphoma: Implication for the development of selective inhibitors', British Journal of Haematology, vol. 147, no. 4, pp. 515-525. https://doi.org/10.1111/j.1365-2141.2009.07887.x
Gloghini, Annunziata ; Buglio, Daniela ; Khaskhely, Noor M. ; Georgakis, Georgios ; Orlowski, Robert Z. ; Neelapu, Sattva S. ; Carbone, Antonino ; Younes, Anas. / Expression of histone deacetylases in lymphoma : Implication for the development of selective inhibitors. In: British Journal of Haematology. 2009 ; Vol. 147, No. 4. pp. 515-525.
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