BCL11B suppression does not influence CD34+ cell differentiation and proliferation
BCL11B suppression does not influence CD34+ cell differentiation and proliferation
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BCL11B 抑制不影响 CD34+ 细胞分化和增殖
DOI：
10.1179/1024533212z.000000000145
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发表时间：
2012-11
期刊：
影响因子：
1.9
通讯作者：
黄欣(共同第一）
中科院分区：
文献类型：
--
作者：
黄欣(共同第一）
b细胞慢性淋巴细胞白血病(CLL)/淋巴瘤11B （BCL11B）基因在t细胞分化和增殖中起关键作用。然而，人们对BCL11B在人造血干细胞/祖细胞中的作用知之甚少。小干扰RNA （siRNA）介导的BCL11B抑制可诱导人t细胞急性淋巴细胞白血病细胞凋亡。为了进一步表征BCL11B在造血干细胞/祖细胞中的作用并评估sirna介导的靶向治疗的安全性，我们研究了BCL11B- sirna935治疗后CD34+细胞的体外分化和增殖。采用磁活化细胞分选技术对3例脐带血中的CD34+细胞进行分选，并用流式细胞术对其纯度进行鉴定。通过核转染将BCL11B- sirna935传递至CD34+细胞，通过实时定量聚合酶链反应分析BCL11B的表达水平。采用甲基纤维素半固体培养法对bcl11b - sirna935处理的CD34+细胞进行红细胞爆发形成单位（BFU-E）、粒细胞/巨噬细胞集落形成单位（CFU-GM）和巨核细胞集落形成单位（CFU-Meg）的评估。BCL11B在CD34+细胞中的表达水平明显低于健康人的Molt-4细胞和外周血单核细胞。转染BCL11B- sirna935后24小时，观察到BCL11B mRNA水平大约降低了1倍。然而，bcl11b - sirna935处理组和模拟转染组对CD34+细胞的集落形成能力无显著差异（P < 0.05）。RNA干扰抑制BCL11B对CD34+细胞的分化和增殖无明显影响。总之，本研究中使用的BCL11B- sirna935可能是安全的，BCL11B可能被认为是t细胞恶性肿瘤靶向基因治疗的新候选药物。
Abstract The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B (BCL11B) gene plays a critical role in T-cell differentiation and proliferation. However, little is understood about the role of BCL11B in human hematopoietic stem/progenitor cells. Small interfering RNA (siRNA)-mediated suppression of the BCL11B was shown to induce apoptosis in human T-cell acute lymphoblastic leukemia cells. To further characterize the role of BCL11B in hematopoietic stem/progenitor cells and assess the safety of siRNA-mediated targeted therapy, the in vitro differentiation and proliferation of CD34+ cells after BCL11B-siRNA935 treatment were studied. CD34+ cells were sorted from three cases of umbilical cord blood by the magnetic activated cell sorting technique, and the purity was identified by flow cytometry. BCL11B-siRNA935 was delivered into CD34+ cells by nucleofection and the BCL11B expression level was analyzed by quantitative real-time polymerase chain reaction. Erythroid burst-forming units (BFU-E), granulocyte/macrophage colony-forming units (CFU-GM), and megakaryocyte colony-forming units (CFU-Meg) were assessed using BCL11B-siRNA935-treated CD34+ cells by the methylcellulose semi-solid culture method. The BCL11B expression level in CD34+ cells was significantly lower than that in Molt-4 cells and peripheral blood mononuclear cells from healthy individuals. An approximate one-fold reduction in the BCL11B mRNA level was observed 24 hours post-transfection with BCL11B-siRNA935. However, there was no significant difference on the colony formation ability of BFU-E, CFU-GM, and CFU-Meg for CD34+ cells between the BCL11B-siRNA935-treated and mock-transfected groups (P > 0.05). BCL11B suppression by RNA interference had no significant influence on the differentiation and proliferation of CD34+ cells. In conclusion, the BCL11B-siRNA935 used in this study may be safe, and BCL11B may be considered a new candidate for targeted gene therapy in T-cell malignancies.
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DOI：
10.1016/j.bbrc.2006.12.155
发表时间：
2007-02
影响因子：
3.1
作者：
Hee-Young Yang;Suehee Kim;Seok-Ho Kim;Dong-Jun Kim;Sun-Uk Kim;Dae-Yeul Yu;Y. Yeom;Dong-Seok Lee;Yong-jun Kim;Byung-Ju Park;Tae-Hoon Lee
通讯作者：
Hee-Young Yang;Suehee Kim;Seok-Ho Kim;Dong-Jun Kim;Sun-Uk Kim;Dae-Yeul Yu;Y. Yeom;Dong-Seok Lee;Yong-jun Kim;Byung-Ju Park;Tae-Hoon Lee
影响因子：
20.3
作者：
Cismasiu, Valeriu B.;Ghanta, Sailaja;Avram, Dorina
通讯作者：
Avram, Dorina
影响因子：
4.1
作者：
Avram, D;Fields, A;Leid, M
通讯作者：
Leid, M
影响因子：
5.2
作者：
Ailyn Choo;P. Palladinetti;T. Holmes;S. Basu;S. Shen;R. Lock;T. O'Brien;G. Symonds;A. Dolnikov
通讯作者：
Ailyn Choo;P. Palladinetti;T. Holmes;S. Basu;S. Shen;R. Lock;T. O'Brien;G. Symonds;A. Dolnikov
影响因子：
11.2
作者：
S. Nagel;M. Kaufmann;H. Drexler;R. MacLeod
通讯作者：
S. Nagel;M. Kaufmann;H. Drexler;R. MacLeod