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Novel agents have been developed targeting the signaling enzymes spleen tyrosine kinase (SYK), Bruton\u2019s tyrosine kinase, and phosphoinositide 3-kinase delta. This review discusses the rationale for targeting these enzymes, as well as the preclinical and clinical evidence supporting their role as therapeutic targets, with a particular focus on SYK inhibition with entospletinib.<\/jats:p>","DOI":"10.1177\/2040620716636542","type":"journal-article","created":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T21:59:59Z","timestamp":1458251999000},"page":"157-170","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":33,"title":["Targeting B-cell receptor signaling kinases in chronic lymphocytic leukemia: the promise of entospletinib"],"prefix":"10.1177","volume":"7","author":[{"given":"Jeff","family":"Sharman","sequence":"first","affiliation":[{"name":"Willamette Valley Cancer Institute and Research Center, US Oncology Research, 3377 Riverbend Drive, Suite 500, Springfield, OR 97477, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Di Paolo","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,3,17]]},"reference":[{"key":"bibr1-2040620716636542","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500461"},{"key":"bibr2-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2879"},{"key":"bibr3-2040620716636542","first-page":"5123","volume":"126","author":"Axelrod M.","year":"2015","journal-title":"Blood (ASH Annual Meeting)"},{"key":"bibr4-2040620716636542","first-page":"121","volume":"33","author":"Barr P.","year":"2015","journal-title":"Hematol Oncol (ICML Annual Meeting)"},{"key":"bibr5-2040620716636542","first-page":"800","volume":"124","author":"Bartlett N.","year":"2014","journal-title":"Blood (ASH Annual Meeting)"},{"key":"bibr6-2040620716636542","first-page":"489","volume":"126","author":"Bojarczuk K.","year":"2015","journal-title":"Blood (ASH Annual Meeting)"},{"key":"bibr7-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-233692"},{"key":"bibr8-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4252"},{"key":"bibr9-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-170415"},{"key":"bibr10-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509388"},{"key":"bibr11-2040620716636542","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1484"},{"key":"bibr12-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400376"},{"key":"bibr13-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-606038"},{"key":"bibr14-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215637"},{"key":"bibr15-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-333682"},{"key":"bibr16-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1038\/ni1036"},{"key":"bibr17-2040620716636542","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2015.33.18_suppl.lba7005"},{"key":"bibr18-2040620716636542","unstructured":"Chang B., Buggy J., Steggerda S. 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