The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia

Blunt Matthew D.; Koehrer Stefan; Dobson Rachel C.; Larrayoz Marta; Wilmore Sarah; Hayman Alice; Parnell Jack; Smith Lindsay D.; Davies Andrew; Johnson Peter W. M.; Conley Pamela B.; Pandey Anjali; Strefford Jonathan C.; Stevenson Freda K.; Packham Graham; Forconi Francesco; Coffey Greg P.; Burger Jan A.; Steele Andrew J.

首页> 外文期刊>Clinical cancer research: an official journal of the American Association for Cancer Research >The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia

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The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia

机译：双Syk / Jak抑制剂Cerdulatinib拮抗B细胞受体和微环境信号在慢性淋巴细胞白血病中

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Purpose: B-cell receptor (BCR)-associated kinase inhibitors, such as ibrutinib, have revolutionized the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative, and resistance is already emerging in a proportion of patients. IL4, expressed in CLL lymph nodes, can augment BCR signaling and reduce the effectiveness of BCR kinase inhibitors. Therefore, simultaneous targeting of the IL4-and BCR signaling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients.

机译：目的：B细胞受体（BCR） - 如易替尼的激酶抑制剂，彻底改变了慢性淋巴细胞白血病（CLL）的治疗。然而，这些药剂不是治愈性的，并且抗性已经出现在一定比例的患者。 IL4在CLL淋巴结中表达，可以增强BCR信号传导并降低BCR激酶抑制剂的有效性。因此，Cerdulatinib的IL4-and BCR信号通路同时靶向，目前在临床试验中的新型双SYK / JAK抑制剂（NCT01994382），可以改善患者的治疗反应。

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《Clinical cancer research: an official journal of the American Association for Cancer Research》 |2017年第9期|共12页
作者
Blunt Matthew D.; Koehrer Stefan; Dobson Rachel C.; Larrayoz Marta; Wilmore Sarah; Hayman Alice; Parnell Jack; Smith Lindsay D.; Davies Andrew; Johnson Peter W. M.; Conley Pamela B.; Pandey Anjali; Strefford Jonathan C.; Stevenson Freda K.; Packham Graham; Forconi Francesco; Coffey Greg P.; Burger Jan A.; Steele Andrew J.;
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Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Texas MD Anderson Canc Ctr Dept Leukemia Div Canc Med Houston TX 77030 USA;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Portola Pharmaceut San Francisco CA USA;

Portola Pharmaceut San Francisco CA USA;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

Portola Pharmaceut San Francisco CA USA;

Univ Texas MD Anderson Canc Ctr Dept Leukemia Div Canc Med Houston TX 77030 USA;

Univ Southampton Canc Sci Unit MP824 Southampton Hants England;

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正文语种 eng
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1. The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia [J] . Blunt Matthew D., Koehrer Stefan, Dobson Rachel C., Clinical cancer research: an official journal of the American Association for Cancer Research . 2017,第9期

机译：双Syk / Jak抑制剂Cerdulatinib拮抗B细胞受体和微环境信号在慢性淋巴细胞白血病中
2. SYK inhibition thwarts the BAFF - B-cell receptor crosstalk and thereby antagonizes Mcl-1 in chronic lymphocytic leukemia [J] . Cody Paiva, Taylor A. Rowland, Bhargava Sreekantham, Haematologica . 2017,第11期

机译：SYK抑制阻止了BAFF-B细胞受体的串扰，从而拮抗慢性淋巴细胞白血病中的Mcl-1。
3. Stimulation of the B-cell receptor activates the JAK2/STAT3 signaling pathway in chronic lymphocytic leukemia cells [J] . RozovskiU., WuJ.Y., HarrisD.M., Blood: The Journal of the American Society of Hematology . 2014,第24期

机译：B细胞受体的刺激在慢性淋巴细胞白血病细胞中激活JAK2 / Stat3信号通路
4. A Structural Equation Modeling Approach of the Toll-Like Receptor Signaling Pathway in Chronic Lymphocytic Leukemia [C] . Tsanousa Athina, Angelis Lefteris, Ntoufa Stavroula, International Workshop on Database and Expert Systems Applications . 2013

机译：慢性淋巴细胞白血病类似收费受体信号通路的结构方程建模方法
5. Omega-3 fatty acids as therapeutic options for the treatment of B-cell chronic lymphocytic leukemia. [D] . Fahrmann, Johannes Francois. 2013

机译：Omega-3脂肪酸可作为治疗B细胞慢性淋巴细胞性白血病的治疗选择。
6. The dual Syk/JAK inhibitor cerdulatinib antagonises B-cell receptor and microenvironmental signaling in chronic lymphocytic leukemia [O] . Matthew D Blunt, Stefan Koehrer, Rachel Dobson, -1

机译：双重Syk / JAK抑制剂cerdulatinib拮抗慢性淋巴细胞白血病中的B细胞受体和微环境信号传导
7. The dual Syk/JAK inhibitor cerdulatinib antagonizes b-cell receptor and microenvironmental signaling in chronic lymphocytic leukemia [O] . Blunt, Matthew D., Koehrer, Stefan, Dobson, Rachel C., 2017

机译：双syk / JaK抑制剂cerdulatinib拮抗慢性淋巴细胞白血病中的b细胞受体和微环境信号

The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia

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