TSLP as a Potential Therapy in the Treatment of CRLF2 B Cell Acute Lymphoblastic Leukemia.
TSLP as a Potential Therapy in the Treatment of CRLF2 B Cell Acute Lymphoblastic Leukemia.
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DOI：
10.3390/ijms24010474
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发表时间：
2022-12-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
细胞因子受体样因子2 B细胞急性淋巴细胞白血病（CRLF 2 B-ALL）是一种高危亚型，其特征是CRLF 2过度表达，儿童和成人的生存率很低。CRLF 2和白细胞介素-7受体α（IL-7 R α）形成细胞因子胸腺基质淋巴细胞生成素（TSLP）的受体，TSLP诱导JAK/STAT和PI 3 K/AKT/mTOR通路信号。我们小组以前的研究表明，低TSLP剂量增加了STAT 5，AKT和S6磷酸化，并有助于CRLF 2 B-ALL细胞存活。我们在体外和体内研究了TSLP在CRLF 2 B-ALL细胞存活和增殖中的作用。我们假设高剂量TSLP增加CRLF 2信号，并有助于CRLF 2 B-ALL细胞在体外和体内增殖增加。有趣的是，我们观察到了相反的效果。具体而言，高剂量TSLP在体外诱导人CRLF 2 B-ALL细胞系的凋亡，阻止CRLF 2 B-ALL细胞的植入，并延长+TSLP患者来源的异种移植小鼠的存活。从机制上讲，我们发现高剂量的TSLP在体外诱导其受体和CRLF 2信号的丢失。这些结果表明，高剂量的TSLP可以进一步研究作为治疗CRLF 2 B-ALL的潜在疗法。
Cytokine receptor-like factor 2 B-cell acute lymphoblastic leukemia (CRLF2 B-ALL) is a high-risk subtype characterized by CRLF2 overexpression with poor survival rates in children and adults. CRLF2 and interleukin-7 receptor alpha (IL-7Rα) form a receptor for the cytokine thymic stromal lymphopoietin (TSLP), which induces JAK/STAT and PI3K/AKT/mTOR pathway signals. Previous studies from our group showed that low TSLP doses increased STAT5, AKT, and S6 phosphorylation and contributed to CRLF2 B-ALL cell survival. Here we investigated the role of TSLP in the survival and proliferation of CRLF2 B-ALL cells in vitro and in vivo. We hypothesized that high doses of TSLP increase CRLF2 signals and contribute to increased proliferation of CRLF2 B-ALL cells in vitro and in vivo. Interestingly, we observed the opposite effect. Specifically, high doses of TSLP induced apoptosis in human CRLF2 B-ALL cell lines in vitro, prevented engraftment of CRLF2 B-ALL cells, and prolonged the survival of +TSLP patient-derived-xenograft mice. Mechanistically, we showed that high doses of TSLP induced loss of its receptor and loss of CRLF2 signals in vitro. These results suggest that high doses of TSLP could be further investigated as a potential therapy for the treatment of CRLF2 B-ALL.
DOI：
10.4049/jimmunol.0900181
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ramalingam TR;Pesce JT;Mentink-Kane MM;Madala S;Cheever AW;Comeau MR;Ziegler SF;Wynn TA
通讯作者：
Wynn TA