Increased histone deacetylase 6 expression serves as a favorable prognostic factor for diffuse large B-cell lymphoma

Abstract

ObjectiveThis study aims to investigate ectopic expression of histone deacetylase 6 (HDAC6) in diffuse large B-cell lymphoma (DLBCL).MethodsThis study analyzed patients with DLBCL (n=132) and reactive lymph node hyperplasia (n=32) diagnosed in our hospital from December 2007 to May 2016. Correlation between HDAC6 expression and clinical pathologic features was analyzed by χ2 test. The significant differences between the 5-year overall survival (OS) or progression-free survival (PFS) and high HDAC6 expression as well as DLBCL clinic-pathological features including age, International Prognostic Index (IPI) score, Eastern Cooperative Oncology Group score, lactate dehydrogenase (LDH), and germinal center B-cell-like were assessed by univariate and multivariate analyses.ResultsHDAC6 high-expression percentage in DLBCL was significantly higher than that in the control group. The proportion of IPI score of 0–2, 5-year OS, and PFS in the high-expression group, which had lower percentage of patients with increased LDH and β2-microglobulin, were significantly higher than those in the low-expression group. Moreover, HDAC6 mRNA expression in HDAC6 protein low expression was markedly lower than that in protein high expression. The multivariate analysis demonstrated that HDAC6 high expression was an independent prognostic factor for patients with DLBCL.ConclusionHDAC6 high expression might be a prognostic factor for DLBCL.

Ibrutinib Resistance Mechanisms and Treatment Strategies for B-Cell Lymphomas

“…Various groups have reported elevated expression of chromatin modifiers HDACs particularly HDAC6 in B-cell lymphomas compared to normal B-cells which can be directly correlated with disease progression. Inhibition of HDAC6 with selective inhibitor provided survival benefits to CLL in euTCL1 mouse model [173,174]. Importantly, inhibition of HDAC and PI3K signaling together with CUDC-907, a dual HDAC-PI3K inhibitor showed profound activity in ibrutinib-resistant MCL cell lines and PDX mouse models [175].…”

Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma

“…Similarly, high mRNA and/or protein HDAC6 expression levels are noted in esophageal squamous cell cancer, pancreatic cancer and lung adenocarcinoma [ 94 , 95 , 96 ]. In contrast, immunohistochemistry (IHC) analysis revealed that in diffuse large B-cell lymphoma (DLBCL) and breast cancer, high HDAC6 expression correlated with better overall, progression-free and disease-free survival, respectively; and overall survival in high-grade serous ovarian cancer (HGSOC) [ 97 , 98 , 99 ]. However, Yano et al reported that IHC analysis of advanced HGSOC patient samples, high HDAC6 expression was associated with poorer overall and progression free survival [ 100 ].…”