Advances in the understanding of molecular genetics and therapy of Richter transformation in chronic lymphocytic leukemia.

IF 2.2 4区 医学 Q3 HEMATOLOGY Leukemia & Lymphoma Pub Date : 2024-12-01 Epub Date: 2024-09-02 DOI:10.1080/10428194.2024.2398660
Marina Deodato, Anna Maria Frustaci, Arianna Zappaterra, Alberto Rapella, Carlo Gambacorti-Passerini, Roberto Cairoli, Marco Montillo, Alessandra Tedeschi
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Abstract

Richter's transformation (RT) is defined as the evolution of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. This complication is rare and aggressive, with poor prognosis and dismal survival. Clonal relationship with the underlying CLL/SLL, observed in ∼80% of cases, represents one of the main factors affecting prognosis. Treatment has been historically based on chemoimmunotherapy, but frequent mutations in genes involved in cell survival and proliferation-such as TP53, NOTCH1, MYC, CDKN2A-confer resistance to standard treatments. During the last years, advances in the knowledge of the biological mechanisms underlying RT allowed to identify genetic and molecular lesions that can potentially be targeted by novel selective agents. Pathway and checkpoint inhibitors, bispecific antibodies and CAR T-cell therapy are currently under investigation and represent promising treatment options. This review summarizes current biological evidence and available data on novel therapeutic agents.

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对慢性淋巴细胞白血病里氏转化的分子遗传学和治疗的认识取得进展。
里氏转化(RT)是指慢性淋巴细胞白血病(CLL)或小淋巴细胞淋巴瘤(SLL)演变为侵袭性淋巴瘤,最常见的是弥漫大 B 细胞淋巴瘤。这种并发症罕见且具有侵袭性,预后差,生存率低。80%的病例与潜在的 CLL/SLL 存在克隆关系,这是影响预后的主要因素之一。治疗方法历来以化学免疫疗法为主,但参与细胞存活和增殖的基因(如 TP53、NOTCH1、MYC、CDKN2A)经常发生突变,从而对标准疗法产生耐药性。在过去几年中,人们对 RT 的生物学机制有了进一步的了解,从而确定了新型选择性药物可能针对的基因和分子病变。通路和检查点抑制剂、双特异性抗体和 CAR T 细胞疗法目前正在研究中,是很有前景的治疗方案。本综述总结了目前有关新型治疗药物的生物学证据和现有数据。
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来源期刊
Leukemia & Lymphoma
Leukemia & Lymphoma 医学-血液学
CiteScore
4.10
自引率
3.80%
发文量
384
审稿时长
1.8 months
期刊介绍: Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor
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