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Abstract 5374: HDAC9 Expression Is Deregulated in Malignant B-Cell Lymphomas in Particular in Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma.

Cubedo, Elena, Gil, Veronica Sylvina, Kim, Chae Hwa, Campuzano-Zuluaga, German, Agarwal, Nitin Kumar, Howell, Louise, Petrie, Kevin R., Vega, Francisco and Zelent, Arthur (2014) Abstract 5374: HDAC9 Expression Is Deregulated in Malignant B-Cell Lymphomas in Particular in Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma. Blood, 124 (21). p. 5374. ISSN 0006-4971

Item Type: Article


Aberrant epigenetics leading to changes in chromatin structure and patterns of gene expression is an important factor in cancer pathogenesis. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme that, within the haematopoietic system, is preferentially expressed in the B-cell lineage. Mice that constitutively express human HDAC9 from early stages of B-cell development, under the control of the immunoglobulin heavy chain (IgH) enhancer, develop lymphoproliferative disorders, including germinal center (GC) and post-GC lymphomas, demonstrating an oncogenic role for HDAC9 in B-cells and highlighting its importance as a therapeutic target. In order to examine the relationship between disease observed in the mouse model and human primary lymphoma, we have examined, using immunohistochemistry (IHC) the expression of full length HDAC9 isoform in a panel of various B-cell malignancies.
The study group included 59 non-Hodgkin lymphomas (NHL), and 3 classical HL. Non-HL consisted of 34 diffuse large B cell lymphoma (DLBCL), 9 follicular lymphoma (FL), 5 marginal zone lymphoma (MZL), 6 mantle cell lymphoma (MCL), and 2 small lymphocytic lymphomas (SLL). HDAC9 expression was assessed by IHC using tissue microarray and/or routine tissue sections. Protein expression was scored as negative (0), low (1), or high (2) depending on the staining signal intensity. Expression of HDAC9 in the nuclei of the tumor cells was compared with that seen in adenocarcinoma cells; if equal or higher, then expression of HDAC9 was considered high and if lower, then expression of HDAC9 was considered low. Five reactive lymph nodes were studied to assess the baseline expression of HDAC9. Rectal adenocarcinomas were used as positive controls. In reactive lymph nodes, HDAC9 was weakly expressed in a subset of germinal center cells, a subset of lymphoid cells in the paracortex as well as in endothelial cells. HDAC9 expression was detected in all subsets of B-cell lymphomas analyzed and in most cases with a level of expression higer than those seen in reactive lymph nodes. DLBCL and MCL tumors have the highest frequency of high HDAC9 expression among the B-cell lymphomas analyzed, 77 and 83% (Fisher’s exact test P=1,0), respectively. No differences in HDAC9 expression were detected in DLBCL of GC and non-GC type. In contrast, most (69%) of the low-grade B cell lymphomas show no or lower expression of HDAC9 (Fisher’s exact test P=0.004; as compared to DLBCL). Classical HL showed frequently low-expression of HDAC9 in the tumor cells. In summary, HDAC9 is frequently expressed in B-cell lymphomas with the highest level of expression found in the most aggressive lymphomas such as DLBCL and MCL. These findings support the biological role of HDAC9 in the pathobiology of aggressive B cell neoplasms.

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Uncontrolled Keywords: b-cell lymphomas, diffuse large b-cell lymphoma, hdac9 gene, mantle-cell lymphoma, lymphoma, adenocarcinoma, cancer, immunoglobulin heavy chains, neoplasms, tumor cells
Depositing User: Kevin Petrie


Item ID: 15812
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ISSN: 0006-4971
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ORCID for Kevin R. Petrie: ORCID iD

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Date Deposited: 22 Mar 2023 15:52
Last Modified: 22 Mar 2023 15:52


Author: Kevin R. Petrie ORCID iD
Author: Elena Cubedo
Author: Veronica Sylvina Gil
Author: Chae Hwa Kim
Author: German Campuzano-Zuluaga
Author: Nitin Kumar Agarwal
Author: Louise Howell
Author: Francisco Vega
Author: Arthur Zelent

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Faculty of Health Sciences and Wellbeing > School of Medicine


Sciences > Biomedical Sciences

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