Molecular classification and therapeutics in diffuse large B-cell lymphoma.
Molecular classification and therapeutics in diffuse large B-cell lymphoma.
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DOI：
10.3389/fmolb.2023.1124360
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发表时间：
2023
影响因子：
5
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弥漫性大B细胞淋巴瘤（DLBCL）包括多种疾病状态，迄今为止已根据免疫组化方法进行了亚组化和表征，其为临床医生提供的预后价值有限，并且治疗方案没有改变。在CHOP治疗中加入利妥昔单抗是治疗方面的最后一次飞跃，但目前的治疗方案遵循标准化的过程，当疾病变得难治时，没有基于基因型的个体化。研究小组正在尝试提出新的策略，根据经常发现的遗传异常对DLBCL进行分类，以更好地预测特定途径失调后的病程，并提供靶向治疗。新算法结合下一代测序技术已经确定了4至7个DLBCL亚组，具体取决于研究团队，这些亚组具有潜在的显著和可操作的遗传改变。针对包括BCR信号传导、NF-κB功能障碍和表观遗传调节在内的通路的各种药物在其各自的组中显示出前景，并且可能显示出作为复发性DLBCL患者的二线或三线治疗的初步效用。亚组的实施将允许收集必要的数据，以确定哪些组是重要的，哪些治疗可能是指征，并将为临床医生和患者提供更好的了解特定的疾病过程。
Diffuse large B-cell lymphoma (DLBCL) encompasses a wide variety of disease states that have to date been subgrouped and characterized based on immunohistochemical methods, which provide limited prognostic value to clinicians and no alteration in treatment regimen. The addition of rituximab to CHOP therapy was the last leap forward in terms of treatment, but regimens currently follow a standardized course when disease becomes refractory with no individualization based on genotype. Research groups are tentatively proposing new strategies for categorizing DLBCL based on genetic abnormalities that are frequently found together to better predict disease course following dysregulation of specific pathways and to deliver targeted treatment. Novel algorithms in combination with next-generation sequencing techniques have identified between 4 and 7 subgroups of DLBCL, depending on the research team, with potentially significant and actionable genetic alterations. Various drugs aimed at pathways including BCR signaling, NF-κB dysfunction, and epigenetic regulation have shown promise in their respective groups and may show initial utility as second or third line therapies to patients with recurrent DLBCL. Implementation of subgroups will allow collection of necessary data to determine which groups are significant, which treatments may be indicated, and will provide better insight to clinicians and patients on specific disease course.