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Bone marrow stromal cells (<jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>) secrete <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12, the ligand for <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4, and protect B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells from cytotoxic drugs. Therefore, the therapeutic use of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 antagonists has been proposed to disrupt cross talk between B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells and the protective stroma. Because <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 antagonists can have activating agonistic function, we compared the genetic and pharmacological deletion of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 in B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells, using <jats:styled-content style=\"fixed-case\">CRISPR<\/jats:styled-content>\u2010Cas9 gene editing and <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 antagonists that are in clinical use (plerixafor, <jats:styled-content style=\"fixed-case\">BKT<\/jats:styled-content>140). Both genetic and pharmacological <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 inhibition significantly reduced B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cell migration to <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12 gradients and beneath <jats:styled-content style=\"fixed-case\">BMSC<\/jats:styled-content>, and restored drug sensitivity to dexamethasone, vincristine and cyclophosphamide. <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102r\u03b3null mice injected with <jats:italic><jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4<\/jats:italic> gene\u2010deleted B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells had significant delay in disease progression and superior survival when compared to control mice injected with <jats:italic><jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4<\/jats:italic> wild\u2010type B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> cells. These findings indicate that anti\u2010leukaemia activity of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 antagonists is primarily due to <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 inhibition, rather than agonistic activity, and corroborate that <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 is an important target to overcome stroma\u2010mediated drug resistance in B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.14075","type":"journal-article","created":{"date-parts":[[2016,4,13]],"date-time":"2016-04-13T06:51:35Z","timestamp":1460530295000},"page":"425-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Effects of pharmacological and genetic disruption of CXCR4 chemokine receptor function in B\u2010cell acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"174","author":[{"given":"Shubhchintan","family":"Randhawa","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung S.","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center Houston TX USA"},{"name":"Department of Haematology Catholic Blood and Marrow Transplantation Centre Cancer Research Institute Seoul St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipanjan","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Lymphoma The University of Texas M. 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Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Sivina","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Koehrer","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"M\u00fcschen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of California San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amnon","family":"Peled","sequence":"additional","affiliation":[{"name":"Goldyne Savad Institute of Gene Therapy Hadassah Hebrew University Hospital Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Lymphoma The University of Texas M. 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Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Konopleva","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A.","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas M.D. Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12883"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70580-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.3.1101"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401729"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-379040"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3182"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.299"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.11.3658"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4918"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.5.1658"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-018192"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402998"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404684"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26113"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2333"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9448"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.9.2370.2370"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085926"},{"key":"e_1_2_8_21_1","first-page":"1","article-title":"Deaths: final data for 2010","volume":"61","author":"Murphy S.L.","year":"2013","journal-title":"National Vital Statistics Reports"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14726"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/382635a0"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009175"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162123"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5403.845"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.05.002"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21208"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12205"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2407"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307850200"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200889200"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.14075","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.14075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T12:23:59Z","timestamp":1696335839000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.14075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,12]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1111\/bjh.14075"],"URL":"https:\/\/doi.org\/10.1111\/bjh.14075","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,12]]},"assertion":[{"value":"2015-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}