Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma
Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma
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利妥昔单抗联合 CHOP (R-CHOP) 克服了弥漫性大 B 细胞淋巴瘤患者与 PRDM1 相关的化疗耐药性
DOI：
10.1182/blood-2006-09-049189
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发表时间：
2007-07-01
期刊：
影响因子：
20.3
通讯作者：
Zhao, Wei-Li
中科院分区：
文献类型：
--
作者：
Liu, Yan-Yan;Leboeuf, Christophe;Zhao, Wei-Li
正调控域I （PRDM1）是成熟B淋巴细胞向浆细胞分化的主要调控因子。PRDM1有2种亚型，PRDM1 α和PRDM1 β，受转录调节核因子κ b - κ b的调控。PRDM1蛋白的表达最近在具有侵袭性行为的弥漫性大b细胞淋巴瘤（DLBCL）的一个亚群中得到证实，这种淋巴瘤现在广泛适用于美罗华联合化疗（R-CHOP）。采用激光显微解剖联合逆转录聚合酶链反应（RT-PCR）技术检测82例DLBCL患者PRDM1基因的表达。结果显示，PRDM1 α和PRDM1 β转录本仅在DLBCL非生发中心b细胞样（non-GCB）亚型的微解剖淋巴瘤细胞中表达。PRDM1 β基因表达与CHOP治疗的非gcb患者的短生存时间相关，而与R-CHOP治疗无关。在体外，耐化疗的b淋巴瘤细胞表达PRDM1 β。利妥昔单抗抑制PRDM1 β的表达，同时伴有nf - κ B失活。因此，可以考虑PRDM1 β表达作为非gcb DLBCL预后标志物的价值。本研究证实了利妥昔单抗治疗DLBCL的有效性，并对其生物学作用有了更好的了解。
The positive regulatory domain I (PRDM1) is a master regulator in the differentiation of mature B lymphocytes to plasma cells. It has 2 isoforms, PRDM1 alpha and PRDM1 beta, and is regulated by the transcriptional regulator nuclear factor kappa (NF)-kappa B. PRDM1 protein expression was recently demonstrated in a subset of diffuse large B-cell lymphoma (DLBCL) with aggressive behavior, a type of lymphoma for which rituximab associated with chemotherapy (R-CHOP) is now widely indicated. Using laser microdissection combined with reverse transcriptionpolymerase chain reaction (RT-PCR) amplification, PRDM1 gene expression was assessed in 82 DLBCL patients. The results showed that both PRDM1 alpha and PRDM1 beta transcripts were expressed in microdissected lymphoma cells only in the non-germinal center B-cell-like (non-GCB) subtype of DLBCL. PRDM1 beta gene expression was correlated with short survival time in the non-GCB patients treated with CHOP but not with R-CHOP. In vitro, B-lymphoma cells resistant to chemotherapy expressed PRDM1 beta. Rituximab suppressed PRDM1 beta expression, which was concomitant with NF-kappa B inactivation. The value of PRDM1 beta expression as a prognostic marker in non-GCB DLBCL might thus be considered. This study confirms the efficiency of rituximab on DLBCL and allows a better understanding of one of its biologic actions.