Bortezomib-resistant nuclear factor κB expression in stem-like cells in mantle cell lymphoma.
Bortezomib-resistant nuclear factor κB expression in stem-like cells in mantle cell lymphoma.
复制标题
DOI：
10.1016/j.exphem.2011.10.004
复制
发表时间：
2012-02
影响因子：
2.6
通讯作者：
McCarty, Nami
中科院分区：
文献类型：
--
作者：
Jung, Hyun Joo;Chen, Zheng;Fayad, Luis;Wang, Michael;Romaguera, Jorge;Kwak, Larry W.;McCarty, Nami
套细胞淋巴瘤(MCL)是B细胞性非霍奇金淋巴瘤(NHL)的一个亚型，约占所有淋巴瘤的6%。与对化疗相对敏感的小淋巴细胞性淋巴瘤和慢性淋巴细胞性淋巴瘤不同，MCL对大多数化疗都高度耐药，是NHL患者中存活率最低的。MCL中的干细胞样细胞，我们称之为套细胞淋巴瘤起始细胞(MCL-ICs)，在缺乏原型B细胞标志物CD19的人群中丰富。这些细胞在连续移植后能够自我更新，并且具有很高的致瘤性。重要的是，这些干细胞样细胞对MCL具有化疗耐药性。在这份报告中，我们发现，尽管结构性核因子-κB(NF-κB)表达，但干细胞样MCL-IC对Bortezomib以及含有Bortezomib的化疗方案具有耐药性。有趣的是，硼替佐米诱导浆样细胞分化为MCL-IC，并上调CD38和CD138的表达。这一过程伴随着浆细胞分化转录因子BLIMP-1和IRF4的表达。本文首次证明干细胞样微淋巴细胞系利用结构性的NF-κB表达来维持生存。鉴于MCL-IC中NF-κB的表达对硼替佐米具有耐药性，寻找替代的治疗策略来抑制NF-κB的表达将是重要的。
Mantle cell lymphoma (MCL) is a subtype of B-cell Non-Hodgkin's Lymphoma (NHL) and accounts for approximately 6% of all lymphomas. Unlike small lymphocytic lymphoma and chronic lymphocytic lymphoma, which are relatively sensitive to chemotherapy, MCL is highly refractory to most chemotherapy, and has the worst survival rate among NHL patients. Stem-like cells in MCL, which we have termed mantle cell lymphoma-initiating cells (MCL-ICs), enriched in the population that are lack of prototypic B-cell marker CD19. These cells were able to self-renew upon serial transplantation and are highly tumorigenic. Importantly, these stem-like cells confer chemotherapeutic resistance to MCL. In this report, we show that stem-like MCL-ICs are resistant to bortezomib, as well as chemotherapeutic regimens containing bortezomib, despite constitutive nuclear factor-κB (NF-κB) expression. Interestingly, bortezomib treatment induced MCL-IC differentiation in plasma-like cells with upregulated expression of CD38 and CD138. This process was accompanied by expression of plasma cell differentiation transcriptional factors, BLIMP-1 and IRF4. This article is the first to show that stem-like MCL cells utilize constitutive NF-κB expression for survival. Given that the NF-κB expression in MCL-ICs is resistant to bortezomib, it will be important to find alternative therapeutic strategies to inhibit NF-κB expression.
登录
查看更多内容
影响因子：
20.3
作者：
Guzman, ML;Neering, SJ;Jordan, CT
通讯作者：
Jordan, CT
影响因子：
5.1
作者：
Mounter, PJ;Lennard, AL
通讯作者：
Lennard, AL
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
15.9
作者：
Baldwin, AS
通讯作者：
Baldwin, AS
影响因子：
2.6
作者：
Jung, Hyun Joo;Chen, Zheng;McCarty, Nami
通讯作者：
McCarty, Nami