Epigenetic Aberrations and Targets in Peripheral T-Cell Lymphoma.
Epigenetic Aberrations and Targets in Peripheral T-Cell Lymphoma.
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DOI：
10.1016/j.clml.2022.04.015
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发表时间：
2022-04
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影响因子：
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通讯作者：
Suheil Albert Atallah-Yunes;M. Robertson;Utpal P. Davé
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作者：
Suheil Albert Atallah-Yunes;M. Robertson;Utpal P. Davé
外周T细胞淋巴瘤（PTCL）包括一组不同的侵袭性T细胞和NK细胞淋巴瘤，尽管具有不同的病理生物学和对治疗的反应，但许多亚型共享相同的治疗算法。在发现破坏PTCL某些亚型（如血管免疫母细胞性T细胞淋巴瘤和未另行说明的PTCL（NOS））的表观遗传调节的基因突变方面取得的分子进展可能解释了这组淋巴瘤中观察到的一线CHOP和CHOP样治疗的不良结局和不满意的反应。在这篇文章中，我们解决了主要的基因突变，如IDH 2，TET 2和DNMT 3A在PTCL中看到，并破坏表观遗传调节途径，重点是乙酰化，脱乙酰化和甲基化。由于靶向PTCL中被破坏的表观遗传调节途径的治疗药物可能在不久的将来改变治疗前景，我们将重点介绍已批准用于治疗难治性和/或复发性PTCL的药物，以及在临床试验中评估的用于治疗一线和难治性复发性疾病的关键方案。我们强调确定所讨论的基因突变与对突出显示的治疗药物的反应之间是否存在关联的重要性，以便可以更好地为此类淋巴瘤患者量身定制治疗。
Peripheral T cell lymphomas (PTCL) comprise a diverse group of aggressive T-cell and NK-cell lymphomas with many subtypes sharing same treatment algorithms despite having different pathobiology and responses to treatment. The molecular advances made in discovery of genetic mutations that disrupt epigenetic modulation in some subtypes of PTCL such as angioimmunoblastic T cell lymphoma and PTCL-not otherwise specified (NOS) may explain the poor outcomes and unsatisfactory responses to frontline line CHOP and CHOP-like therapy seen in this group of lymphomas. In this article, we address the main genetic mutations such as IDH2, TET2 and DNMT3A seen in PTCL and that disrupt the epigenetic modulation pathways, focusing on acetylation, deacetylation and methylation. Since therapeutic agents that target the disrupted epigenetic modulation pathways in PTCL may change treatment landscape in the near future, we will highlight the ones approved for treatment of refractory and/or relapsed PTCL and also the pivotal regimens being evaluated in clinical trials for treatment of frontline and refractory relapsed disease. We stress the importance of determining whether there is an association between the discussed genetic mutations and responses to the highlighted therapeutic agents such that treatments could be better tailored in patients with this kind of lymphoma with unmet needs.