Histone Deacetylases (HDACs) Guided Novel Therapies for T-cell lymphomas

Zhang, Qing; Wang, Shaobin; Chen, Junhui; Yu, Zhen

doi:10.7150/ijms.30154

Cited by 67 publications

(43 citation statements)

References 159 publications

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“…As a single agent, the efficacy of romidepsin is generally limited, with an ORR of nearly 25% (shown as a combination Table 5 ). However, when combined with pralatrexate or CHOP, the adverse reactions were not only reduced but also significantly alleviated in PTCL patients, with the ORR reaching 70–80%, which was also consistent with the findings of other reported literature [ 49 ] (shown as Table 3 ).…”

Section: Epigenetic Drugs In Relapsed and Refractory Ptclsupporting

confidence: 91%

“…HDAC inhibitors work by the following two major mechanisms: increasing promoter histone acetylation and inducing transcription factor acetylation [ 47 ]. Consistent with their similar inhibition of the enzyme activity pocket, HDACis seem to have similar toxicity profiles, which include gastrointestinal disturbance, myelosuppression, transient prolongations of QTc interval, nausea, asthenia/fatigue, and infections (all types pooled), although idiosyncratic side effects of particular HDACis have been noted and may relate to differences in chemical structure [ 48 , 49 ]. Most HDAC inhibitors have similar secondary effects that increase histone acetylation in PBMCs.…”

Section: Histone Modification In the Pathogenesis Of Peripheral T-celmentioning

confidence: 99%

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Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma

Zhang

2020

Clin Epigenet

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Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of clinically aggressive diseases associated with poor prognosis. Except for ALK + anaplastic large-cell lymphoma (ALCL), most peripheral T-cell lymphomas are highly malignant and have an aggressive disease course and poor clinical outcomes, with a poor remission rate and frequent relapse after first-line treatment. Aberrant epigenetic alterations play an important role in the pathogenesis and development of specific types of peripheral T-cell lymphoma, including the regulation of the expression of genes and signal transduction. The most common epigenetic alterations are DNA methylation and histone modification. Histone modification alters the level of gene expression by regulating the acetylation status of lysine residues on the promoter surrounding histones, often leading to the silencing of tumour suppressor genes or the overexpression of proto-oncogenes in lymphoma. DNA methylation refers to CpG islands, generally leading to tumour suppressor gene transcriptional silencing. Genetic studies have also shown that some recurrent mutations in genes involved in the epigenetic machinery, including TET2, IDH2-R172, DNMT3A, RHOA, CD28, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300, have been observed in cases of PTCL. The aberrant expression of miRNAs has also gradually become a diagnostic biomarker. These provide a reasonable molecular mechanism for epigenetic modifying drugs in the treatment of PTCL. As epigenetic drugs implicated in lymphoma have been continually reported in recent years, many new ideas for the diagnosis, treatment, and prognosis of PTCL originate from epigenetics in recent years. Novel epigenetic-targeted drugs have shown good tolerance and therapeutic effects in the treatment of peripheral T-cell lymphoma as monotherapy or combination therapy. NCCN Clinical Practice Guidelines also recommended epigenetic drugs for PTCL subtypes as second-line therapy. Epigenetic mechanisms provide new directions and therapeutic strategies for the research and treatment of peripheral T-cell lymphoma. Therefore, this paper mainly reviews the epigenetic changes in the pathogenesis of peripheral T-cell lymphoma and the advancement of epigenetic-targeted drugs in the treatment of peripheral T-cell lymphoma (PTCL).

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Section: Epigenetic Drugs In Relapsed and Refractory Ptclsupporting

confidence: 91%

Section: Histone Modification In the Pathogenesis Of Peripheral T-celmentioning

confidence: 99%

Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma

Zhang

2020

Clin Epigenet

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“…However, the effect is only transient in HAM/TSP patients [ 40 ], and may be related to temporal fluctuations in viral RNA and response to immune control mechanisms in these patients [ 250 , 251 , 252 ]. Improved therapies include VPA combinations with zidovudine (AZT) or cytokines (IFNα) [ 253 , 254 , 255 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Expression and Latency in BLV and HTLV

Pluta

Jaworski

Douville

2020

Viruses

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Human T-lymphotrophic virus type 1 (HTLV-1) and Bovine leukemia virus (BLV) belong to the Deltaretrovirus genus. HTLV-1 is the etiologic agent of the highly aggressive and currently incurable cancer adult T-cell leukemia (ATL) and a neurological disease HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). BLV causes neoplastic proliferation of B cells in cattle: enzootic bovine leucosis (EBL). Despite the severity of these conditions, infection by HTLV-1 and BLV appear in most cases clinically asymptomatic. These viruses can undergo latency in their hosts. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infection, as well as for pathogenesis in vivo. In this review, we will present the mechanisms that control proviral activation and retroviral latency in deltaretroviruses, in comparison with other exogenous retroviruses. The 5′ long terminal repeats (5′-LTRs) play a main role in controlling viral gene expression. While the regulation of transcription initiation is a major mechanism of silencing, we discuss topics that include (i) the epigenetic control of the provirus, (ii) the cis-elements present in the LTR, (iii) enhancers with cell-type specific regulatory functions, (iv) the role of virally-encoded transactivator proteins, (v) the role of repressors in transcription and silencing, (vi) the effect of hormonal signaling, (vii) implications of LTR variability on transcription and latency, and (viii) the regulatory role of non-coding RNAs. Finally, we discuss how a better understanding of these mechanisms may allow for the development of more effective treatments against Deltaretroviruses.

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“…HDACs are divided into four groups: HDAC I (HDAC 1, 2, 3, and 8), HDAC II (HDAC 4, 5, 6, 7, 9, and 10), HDAC III and HDAC IV. 332…”

Section: Idh2mentioning

confidence: 99%

Advances in targeted therapy for malignant lymphoma

Wang

Qin

Huo

et al. 2020

Sig Transduct Target Ther

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The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment. Although these targeted agents have shown great success in treating lymphoma patients, adverse events should be noted. The selection of the most suitable candidates, optimal dosage, and effective combinations warrant further investigation. In this review, we systematically outlined the advances in targeted therapy for malignant lymphoma, providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.Signal Transduction and Targeted Therapy (2020) 5:15; https://doi.

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Histone Deacetylases (HDACs) Guided Novel Therapies for T-cell lymphomas

Cited by 67 publications

References 159 publications

Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma

Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma

Regulation of Expression and Latency in BLV and HTLV

Advances in targeted therapy for malignant lymphoma

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