{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:35:44Z","timestamp":1768563344247,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,4,2]],"date-time":"2013-04-02T00:00:00Z","timestamp":1364860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:p>Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr\u2010Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr\u2010Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr\u2010Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr\u2010Abl is sequestered into vesicular structures that co\u2010localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1\/ATG7). Pharmacological inhibition of autophagy also reduced Bcr\u2010Abl\/LC3 co\u2010localization in both K562 and CML patient cells. Bcr\u2010Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr\u2010Abl protein levels to those of untreated cells. This ability to down\u2010regulate Bcr\u2010Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib. 88:455\u2013462, 2013. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.23428","type":"journal-article","created":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T11:35:10Z","timestamp":1361878510000},"page":"455-462","source":"Crossref","is-referenced-by-count":47,"title":["Induction of autophagy by Imatinib sequesters Bcr\u2010Abl in autophagosomes and down\u2010regulates Bcr\u2010Abl protein"],"prefix":"10.1002","volume":"88","author":[{"given":"Baukje M.","family":"Elzinga","sequence":"first","affiliation":[{"name":"Leslie C. Quick Laboratory Cork Cancer Research Centre, BioSciences Institute, University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle J.","family":"Nyhan","sequence":"additional","affiliation":[{"name":"Leslie C. Quick Laboratory Cork Cancer Research Centre, BioSciences Institute, University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa C.","family":"Crowley","sequence":"additional","affiliation":[{"name":"Leslie C. Quick Laboratory Cork Cancer Research Centre, BioSciences Institute, University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey R.","family":"O'Donovan","sequence":"additional","affiliation":[{"name":"Leslie C. Quick Laboratory Cork Cancer Research Centre, BioSciences Institute, University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary R.","family":"Cahill","sequence":"additional","affiliation":[{"name":"Department of Haematology Cork University Hospital Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon L.","family":"McKenna","sequence":"additional","affiliation":[{"name":"Leslie C. Quick Laboratory Cork Cancer Research Centre, BioSciences Institute, University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,4,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.6.2371.bloodjournal8662371"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.12588"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.12.7587"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.2.1389"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1567"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0076"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-249623"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.89"},{"key":"e_1_2_6_10_1","first-page":"355","article-title":"The heat shock protein 90 antagonist geldanamycin alters chaperone association with p210bcr\u2010abl and v\u2010src proteins before their degradation by the proteasome","volume":"11","author":"An WG","year":"2000","journal-title":"Cell Growth Differ"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402257"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1599207"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1007-1102"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.200"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-261040"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.4.14397"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-402578"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35660"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21914"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402309"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.6.1889"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4800(87)90018-9"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.90.3.665"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.11.002"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-054098"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1080\/10428190290021371","article-title":"Heat shock protein 90\u2010antagonist destabilizes Bcr\u2010Abl\/HSP90 chaperone complex","volume":"43","author":"Shiotsu Y","year":"2002","journal-title":"Leuk Lymph"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2386"},{"key":"e_1_2_6_28_1","first-page":"839","article-title":"The proto\u2010oncogene product p120CBL and the adaptor proteins CRKL and c\u2010CRK link c\u2010ABL, p190BCR\/ABL and p210BCR\/ABL to the phosphatidylinositol\u20103' kinase pathway","volume":"12","author":"Sattler M","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.233"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-10-1092"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.046"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.11.055"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405652200"},{"key":"e_1_2_6_34_1","article-title":"Pharmacological agents with inherent anti-autophagic activity improve the cytotoxicity of Imatinib","author":"Crowley LC","year":"2013","journal-title":"Oncol Rep"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.04.007"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.018"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.23428","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.23428","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T01:29:50Z","timestamp":1700616590000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.23428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,2]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1002\/ajh.23428"],"URL":"https:\/\/doi.org\/10.1002\/ajh.23428","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,2]]}}}