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Gene-expression profile as well as signal pathway and protein analyses revealed that galectin-3 (Gal-3), a member of the \u03b2-gal\u2013binding galectin family of proteins, was specifically induced by coculture with HS-5 cells, a BM stroma cell-derived cell line, in all five CML cell lines examined. It was also found that primary CML cells expressed high levels of Gal-3 in BM. Enforced expression of Gal-3 activated Akt and Erk, induced accumulation of Mcl-1, and promoted in vitro cell proliferation, multidrug resistance to tyrosine kinase inhibitors for Bcr-Abl and genotoxic agents as a result of impaired apoptosis induction, and chemotactic cell migration to HS-5\u2013derived soluble factors in CML cell lines independently of Bcr-Abl tyrosine kinase. The conditioned medium from Gal-3\u2013overexpressing CML cells promoted in vitro cell proliferation of CML cells and HS-5 cells more than did the conditioned medium from parental cells. Moreover, the in vivo study in a mice transplantation model showed that Gal-3 overexpression promoted the long-term BM lodgment of CML cells. These results demonstrate that leukemia microenvironment-specific Gal-3 expression supports molecular signaling pathways for disease maintenance in BM and resistance to therapy in CML. They also suggest that Gal-3 may be a candidate therapeutic target to help overcome BMME-mediated therapeutic resistance.<\/jats:p>","DOI":"10.1073\/pnas.1111138108","type":"journal-article","created":{"date-parts":[[2011,10,11]],"date-time":"2011-10-11T01:31:58Z","timestamp":1318296718000},"page":"17468-17473","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":85,"title":["Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia"],"prefix":"10.1073","volume":"108","author":[{"given":"Mio","family":"Yamamoto-Sugitani","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eishi","family":"Ashihara","sequence":"additional","affiliation":[{"name":"Molecular Cell Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisao","family":"Nagoshi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Shimura","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Kiyota","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuko","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"},{"name":"Departments of bMolecular Hematology and Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Akaji","sequence":"additional","affiliation":[{"name":"Chemistry, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Taki","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics and Therapeutics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Uoshima","sequence":"additional","affiliation":[{"name":"Department of Hematology, Matsushita Memorial Hospital, Osaka 570-8540, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kyoto Second Red Cross Hospital, Kyoto 602-8026, Japan; 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