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Studies have shown that leukemic cells secrete C\u2010chemokine (C\u2010C motif) ligand 3 (CCL3), to disrupt the BMME resulting in loss of hematopoiesis and support of leukemic cell survival and proliferation. In this study, a murine model of blast crisis chronic myelogenous leukemia (bcCML) that expresses the translocation products BCR\/ABL and Nup98\/HoxA9 was used to determine the role of CCL3 in BMME regulation. Leukemic cells derived from CCL3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were shown to minimally engraft in a normal BMME, thereby demonstrating that CCL3 signaling was necessary to recapitulate bcCML disease. Further analysis showed disruption in hematopoiesis within the BMME in the bcCML model. To rescue the altered BMME, therapeutic inhibition of CCL3 signaling was investigated using bone\u2010targeted nanoparticles (NP) to deliver Maraviroc, an inhibitor of C\u2010C chemokine receptor type 5 (CCR5), a CCL3 receptor. NP\u2010mediated Maraviroc delivery partially restored the BMME, significantly reduced leukemic burden, and improved survival. Overall, our results demonstrate that inhibiting CCL3 via CCR5 antagonism is a potential therapeutic approach to restore normal hematopoiesis as well as reduce leukemic burden within the BMME.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000938rr","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T16:43:53Z","timestamp":1615913033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Reduction of leukemic burden via bone\u2010targeted nanoparticle delivery of an inhibitor of C\u2010chemokine (C\u2010C motif) ligand 3 (CCL3) signaling"],"prefix":"10.1096","volume":"35","author":[{"given":"Marian A.","family":"Ackun\u2010Farmmer","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Rochester Rochester NY USA"},{"name":"Department of Orthopaedics and Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia A.","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Rochester Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie L.","family":"Lesch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Rochester Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lila","family":"Yang","sequence":"additional","affiliation":[{"name":"New York Institute of Technology College of Osteopathic Medicine New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Calvi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"},{"name":"Department of Medicine Endocrine Division University of Rochester Medical Center Rochester NY USA"},{"name":"Wilmot Cancer Institute School of Medicine and Dentistry University of Rochester Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle S. 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