Clin Cancer Res:弥漫性大B细胞淋巴瘤（DLBCL）治疗耐药新机制

2019-04-20 肿瘤资讯大家都想看的

弥漫性大B细胞淋巴瘤（DLBCL）是淋巴瘤中最常见的类型，含利妥昔单抗的免疫化疗方案显着改善了患者的总生存，但仍有部分患者=原发耐药或进展或复发，并且预后差，其中对利妥昔单抗的耐药是其预后不良的重要原因。近日，Clinical Cancer Research杂志发表了一项揭示DLBCL利妥昔单抗耐药新机制的研究成果。该研究由河南省肿瘤医院刘艳艳教授团队与中美（河南）荷美尔肿瘤研究院、美国内布拉斯加

弥漫性大B细胞淋巴瘤（DLBCL）是淋巴瘤中最常见的类型，含利妥昔单抗的免疫化疗方案显着改善了患者的总生存，但仍有部分患者=原发耐药或进展或复发，并且预后差，其中对利妥昔单抗的耐药是其预后不良的重要原因。近日，Clinical Cancer Research杂志发表了一项揭示DLBCL利妥昔单抗耐药新机制的研究成果。该研究由河南省肿瘤医院刘艳艳教授团队与中美（河南）荷美尔肿瘤研究院、美国内布拉斯加大学医学中心等单位合作完成。

刘艳艳内科副主任博士硕士生导师，河南省肿瘤医院肿瘤内科副主任，河南省学术技术带头人，淋巴瘤研究所所长，美国Nebraska大学医学中心博士后，郑州大学全额资助博士

临床特色和优势：淋巴结肿大的鉴别诊断、淋巴肿瘤规范治疗和难治患者的个体化治疗、恶性肿瘤淋巴转移的整体化治疗。

背景

DLBCL是最常见的非霍奇金淋巴瘤，具有不同的遗传学异常、生物学特征及预后。利妥昔单抗与标准CHOP（环磷酰胺+多柔比星+长春新碱+泼尼松）化疗方案（R-CHOP）显着改善了患者的总生存（OS），但仍有30%～40％的患者对治疗不敏感或治疗后出现疾病进展，且预后极差。利妥昔单抗耐药是这部分患者预后差的部分原因，利妥昔单抗诱导的钙离子内流是诱导细胞凋亡的重要因子，研究人员探讨了钙通道在利妥昔单抗耐药中的潜在作用。

实验设计

研究人员比较了对R-CHOP方案敏感或耐药的DLBCL患者钙通道成员的独特表达。通过使用细胞系和患者来源的异种移植小鼠模型的体外和体内机制研究，进一步验证这一观察结果。

结果

在两个独立的DLBCL队列中，CACNA1C表达与R-CHOP方案耐药呈显着的负相关，在校正国际预后指数、起源细胞分类和MYC/BCL2 双重表达后，CACNA1C表达是R-CHOP方案耐药的独立预后因子。CACNA1C表达减少了利妥昔单抗诱导的细胞凋亡和肿瘤缩小。研究人员进一步证明了CACNA1C与CD20的直接相互作用及其在CD20稳定中的作用。L型钙通道(L-type calcium channel)的功能调节剂在利妥昔单抗诱导的细胞凋亡和肿瘤抑制中显示出预期的变化。此外，研究人员还证实CACNA1C表达直接受miRNA-363的调节，miRNA-363高表达与DLBCL预后差相关。

结论

研究人员明确了CACNA1C在利妥昔单抗耐药中的作用，调节CACNA1C表达或活性可能改变DLBCL患者对利妥昔单抗的敏感性。

原始出处：

Liu YY， Zhang JY， Zhang PP， Zhou W.et al.L-type cav 1.2 calcium channel-a-1C regulates response to rituximab in diffuse large b-cell lymphoma. Clin Cancer Res. 2019 Mar 1. pii： clincanres.2146.2018. doi： 10.1158/1078-0432.CCR-18-2146http：//clincancerres.aacrjournals.org/content/early/2019/03/01/1078-0432.CCR-18-2146.long

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2019-10-22 marlenexl

#细胞淋巴瘤#

45 0
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2019-07-09 ms7258648636991762

#LBCL#

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2019-04-22 xiaoyeshuang

#B细胞#

47 0
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2019-04-22 bnjfy

#弥漫性大B细胞淋巴瘤#

36 0
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2019-04-22 cathymary

#DLBCL#

39 0
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2019-04-22 zhouqu_8

#弥漫性#

27 0
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2019-04-20 122b9cbbm13暂无昵称

有用评论咿呀

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