Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines

Buglio, David Lo; Georgakis, Georgios V.; Hanabuchi, Shino; Arima, Kazuhiko; Khaskhely, Noor M.; Liu, Yongjun; Younes, Anas

doi:10.1182/blood-2008-01-133769

Cited by 152 publications

(138 citation statements)

References 33 publications

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“…Therefore, histone deacetylase inhibitors became attractive targets to treat HL. It has been demonstrated that in vitro vorinostat, in addition to its direct antitumor activity, alters cytokine balance and shifts toward a favorable Th1 composition through inhibiting STAT6 and decreasing TARC expression [94]. Vorinostat and romidepsin have been approved by the FDA in the treatment of relapsed cutaneous T cell lymphoma.…”

Section: Prospective Therapeutic Solutions and Possibilities Of Targementioning

confidence: 99%

Immunologic pathomechanism of Hodgkin's lymphoma

Jóna

Szodoray

Illés

2013

Experimental Hematology

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Section: Prospective Therapeutic Solutions and Possibilities Of Targementioning

confidence: 99%

Immunologic pathomechanism of Hodgkin's lymphoma

Jóna

Szodoray

Illés

2013

Experimental Hematology

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“…STAT6 has been targeted in the setting of Hodgkin lymphoma via the histone deacetylase inhibitor, vorinostat. 32 This has been shown to inhibit STAT6 phosphorylation and was associated with a decrease in expression of chemokine Thymus and Activation-Regulated Chemokine and cytokine IL-5. Histone deacetylase inhibition is thought to exert antitumor effect via this immune regulation.…”

Section: Modern Pathology (2016) 29 570-581mentioning

confidence: 99%

Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations

et al. 2016

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A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2 translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al. Along with pertinent clinical information, we detail their histopathology, IGH/BCL2 translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well-to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situ hybridization analysis, the vast majority lacked IGH/BCL2 translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14 mutations were identified in three, highlighting the strong association of 1p36/ TNFRSF14 abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6 mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6 mutations is higher than recently reported in conventional follicular lymphoma (11%). These findings lend support for a clinicopathologic variant of t(14;18) negative nodal follicular lymphoma and suggests importance of the interleukin (IL)-4/JAK/STAT6 pathway in this variant.

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“…1 Furthermore, epigenetic analyses are of interest since epigenetic therapy is emerging as a valuable and effective treatment approach for peripheral T-cell lymphomas and is also envisaged for Bcell and Hodgkin's lymphomas. [2][3][4][5] There are different sets of epigenetic instructions involved in the regulation of gene expression. 1 DNA methylation of gene promoters contributes significantly to gene silencing whereas histone modifications such as acetylation of lysine 9 and 14 of histone H3 (H3K9/14 acetylation) are positively correlated with gene activation.…”

Section: Introductionmentioning

confidence: 99%

Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation

Seitz¹,

Thomas²,

Zimmermann³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundEpigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin's lymphoma. However, little is known regarding epigenetic similarities between cells of classical Hodgkin's lymphoma and plasma cell myeloma, both of which share extinction of the gene expression program of mature B cells. Design and MethodsGlobal histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin's lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA polymerase chain reaction for selected genes. Epigenetic modifications were compared to gene expression data. ResultsCharacteristic B-cell genes were hypoacetylated in classical Hodgkin's lymphoma and plasma cell myeloma cell lines as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin' lymphoma and plasma cell myeloma cell lines, such as IRF4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected characteristic B-cell genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin's lymphoma than in plasma cell myeloma. ConclusionsOur epigenetic data support the view that classical Hodgkin's lymphoma is characterized by abortive plasma cell differentiation with a down-regulation of characteristic B-cell genes but without activation of most genes typical of plasma cells.

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Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines

Cited by 152 publications

References 33 publications

Immunologic pathomechanism of Hodgkin's lymphoma

Immunologic pathomechanism of Hodgkin's lymphoma

Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations

Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation

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