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This review highlights critical cellular and molecular pathways of CLL-microenvironment cross-talk. In vitro and in vivo models for studying the CLL microenvironment are discussed, along with their use in searching for therapeutic targets and in drug testing. Clinically, CXCR4 antagonists and small-molecule antagonists of B cell receptor (BCR)-associated kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], and PI3K\u03b4) are the most advanced drugs for targeting specific interactions between CLL cells and the miocroenvironment. Preclinical and first clinical evidence suggests that high-risk CLL patients can particularly benefit from these alternative agents. These findings indicate that interplay between leukemia-inherent and environmental factors, nature and nurture determines disease progression in CLL.<\/jats:p>","DOI":"10.1182\/asheducation-2011.1.96","type":"journal-article","created":{"date-parts":[[2011,12,7]],"date-time":"2011-12-07T20:33:13Z","timestamp":1323289993000},"page":"96-103","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":149,"title":["Nurture versus Nature: The Microenvironment in Chronic Lymphocytic Leukemia"],"prefix":"10.1182","volume":"2011","author":[{"given":"Jan A.","family":"Burger","sequence":"first","affiliation":[{"name":"Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"16","key":"2019111718005789000_B1","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1182\/blood-2009-06-225326","article-title":"The 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