{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:29:24Z","timestamp":1759336164148},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2013,4,25]],"date-time":"2013-04-25T00:00:00Z","timestamp":1366848000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drugs Aging"],"published-print":{"date-parts":[[2013,7]]},"DOI":"10.1007\/s40266-013-0085-9","type":"journal-article","created":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T10:32:49Z","timestamp":1367404369000},"page":"467-477","source":"Crossref","is-referenced-by-count":3,"title":["Management Options for Refractory Chronic Myeloid Leukemia: Considerations for the Elderly"],"prefix":"10.1007","volume":"30","author":[{"given":"Massimo","family":"Breccia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliana","family":"Alimena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,4,25]]},"reference":[{"key":"85_CR1","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMra020777","volume":"349","author":"JM Goldman","year":"2003","unstructured":"Goldman JM, Melo JV. Chronic myeloid leukemia\u2014advances in biology and new approaches to treatment. N Engl J Med. 2003;349:1451\u201364.","journal-title":"N Engl J Med"},{"key":"85_CR2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrm1280","volume":"5","author":"O Hantschel","year":"2004","unstructured":"Hantschel O, Superti-Furga G. Regulation of the c-Abl and Bcr\u2013Abl tyrosine kinases. Nat Rev Mol Cell Biol. 2004;5:33\u201344.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"85_CR3","doi-asserted-by":"crossref","first-page":"207","DOI":"10.7326\/0003-4819-131-3-199908030-00008","volume":"131","author":"S Faderl","year":"1999","unstructured":"Faderl S, Talpaz M, Estrov Z, Kantarjian H. Chronic myelogenous leukemia: biology and therapy. Ann Intern Med. 1999;131:207\u201319.","journal-title":"Ann Intern Med"},{"key":"85_CR4","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.hoc.2004.03.008","volume":"18","author":"JV Melo","year":"2004","unstructured":"Melo JV, Deininger MW. Biology of chronic myelogenous leukemia-signaling pathways of initiation and transformation. Hematol Oncol Clin N Am. 2004;18:545\u201368.","journal-title":"Hematol Oncol Clin N Am"},{"key":"85_CR5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/shem.2003.50034","volume":"40","author":"M Sattler","year":"2003","unstructured":"Sattler M, Griffin JD. Molecular mechanisms of transformation by the BCR\u2013ABL oncogene. Semin Hematol. 2003;40:4\u201310.","journal-title":"Semin Hematol"},{"key":"85_CR6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1615\/CritRevOncog.v17.i1.30","volume":"17","author":"DT Yeung","year":"2012","unstructured":"Yeung DT, Hughes TP. Therapeutic targeting of BCR\u2013ABL: prognostic markers of response and resistance mechanism in chronic myeloid leukemia. Crit Rev Oncog. 2012;17:17\u201330.","journal-title":"Crit Rev Oncog"},{"key":"85_CR7","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/cncr.11520","volume":"98","author":"G Garcia-Manero","year":"2003","unstructured":"Garcia-Manero G, Faderl S, O\u2019Brien S, Cortes J, Talpaz M, Kantarjian HM. Chronic myelogenous leukaemia: a review and update of therapeutic strategies. Cancer. 2003;98:437\u201357.","journal-title":"Cancer"},{"key":"85_CR8","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1056\/NEJM200104053441401","volume":"344","author":"BJ Druker","year":"2001","unstructured":"Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR\u2013ABL tyrosine kinase in chronic myeloid leukaemia. N Engl J Med. 2001;344:1031\u20137.","journal-title":"N Engl J Med"},{"key":"85_CR9","first-page":"1972","volume":"9","author":"JR Johnson","year":"2003","unstructured":"Johnson JR, Bross P, Cohen M, et al. Approval summary: imatinib mesylate capsules for treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukaemia in chronic phase. Clin Cancer Res. 2003;9:1972\u20139.","journal-title":"Clin Cancer Res"},{"key":"85_CR10","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1182\/blood-2004-08-3097","volume":"105","author":"MW Deininger","year":"2005","unstructured":"Deininger MW, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukaemia. Blood. 2005;105:2640\u201353.","journal-title":"Blood"},{"key":"85_CR11","doi-asserted-by":"crossref","unstructured":"O\u2019Brien SG, Guilhot F, Goldman JM, et al. International randomized study of interferon versus STI571 (IRIS) 7-year follow-up: sustained survival, low rate of transformation and increased rate of major molecular response (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CMLCP) treated with imatinib (IM). Blood. 2008;112:abstr 186.","DOI":"10.1182\/blood.V112.11.186.186"},{"key":"85_CR12","doi-asserted-by":"crossref","unstructured":"Deininger MW, O\u2019Brien SG, Guilhot F, et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow-up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood. 2009;114:abstr 1126.","DOI":"10.1182\/blood.V114.22.1126.1126"},{"key":"85_CR13","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1182\/blood-2006-02-005686","volume":"108","author":"M Baccarani","year":"2006","unstructured":"Baccarani M, Saglio G, Goldman J, European LeukemiaNet, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809\u201320.","journal-title":"Blood"},{"key":"85_CR14","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.1200\/JCO.2009.25.0779","volume":"27","author":"M Baccarani","year":"2009","unstructured":"Baccarani M, Cortes J, Pane F, European LeukemiaNet, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27:6041\u201351.","journal-title":"J Clin Oncol"},{"issue":"Suppl 1","key":"85_CR15","doi-asserted-by":"crossref","first-page":"i52","DOI":"10.1093\/annonc\/mdi807","volume":"16","author":"B Simonsson","year":"2005","unstructured":"Simonsson B, Kloke O, Stahel RA, ESMO Guidelines Task Force. ESMO minimum clinical recommendations for the diagnosis, treatment and follow-up of chronic myelogenous leukemia (CML). Ann Oncol. 2005;16(Suppl 1):i52\u20133.","journal-title":"Ann Oncol"},{"issue":"Suppl 1","key":"85_CR16","first-page":"S29","volume":"1","author":"SM O\u2019Brien","year":"2003","unstructured":"O\u2019Brien SM, Kantarjian H, Radich J. Update: chronic myelogenous leukemia clinical practice guidelines. J Natl Compr Cancer Netw. 2003;1(Suppl 1):S29\u201340.","journal-title":"J Natl Compr Cancer Netw"},{"key":"85_CR17","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/cncr.11629","volume":"98","author":"J Cortes","year":"2003","unstructured":"Cortes J, Talpaz M, O\u2019Brien S, et al. Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer. 2003;98:1105\u201313.","journal-title":"Cancer"},{"key":"85_CR18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3324\/haematol.10239","volume":"92","author":"G Rosti","year":"2007","unstructured":"Rosti G, Iacobucci I, Bassi S, et al. Impact of age on the outcome off patients with chronic myeloid leukemia in late chronic phase: results off a phase II study off the GIMEMA CML Working Party. Haematologica. 2007;92:101\u20135.","journal-title":"Haematologica"},{"key":"85_CR19","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/j.leukres.2010.07.001","volume":"34","author":"R Latagliata","year":"2010","unstructured":"Latagliata R, Breccia M, Carmosino I, et al. \u201cReal-life\u201d results of front-line treatment with imatinib in older patients (>65\u00a0years) with newly diagnosed chronic myelogenous leukemia. Leuk Res. 2010;34:1472\u20135.","journal-title":"Leuk Res"},{"key":"85_CR20","unstructured":"Pletsch N, Lauseker M, Saussele S, et al. Therapy with imatinib in elderly CML patients (>65\u00a0years) is well tolerated but cytogenetic and molecular remissions seem to be achieved later compared to younger patients. Haematologica. 2009;94:253 abstr 0625."},{"key":"85_CR21","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/jnci\/djr060","volume":"103","author":"C Gambacorti-Passerini","year":"2011","unstructured":"Gambacorti-Passerini C, Antolini L, Mahon FX, et al. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst. 2011;103:553\u201361.","journal-title":"J Natl Cancer Inst"},{"key":"85_CR22","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1053\/j.seminhematol.2010.06.005","volume":"47","author":"P Rose\u00e8 La","year":"2010","unstructured":"La Rose\u00e8 P, Deininger MW. Resistance to imatinib: mutations and beyond. Semin Hematol. 2010;47:335\u201343.","journal-title":"Semin Hematol"},{"key":"85_CR23","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.blre.2011.09.001","volume":"25","author":"S Roychowdhury","year":"2011","unstructured":"Roychowdhury S, Talpaz M. Managing resistance in chronic myeloid leukemia. Blood Rev. 2011;25:279\u201390.","journal-title":"Blood Rev"},{"key":"85_CR24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1600-0609.2011.01689.x","volume":"87","author":"S Vaidya","year":"2011","unstructured":"Vaidya S, Ghosh K, Vundinti BR. Recent developments in drug resistance mechanism in chronic myeloid leukemia: a review. Eur J Haematol. 2011;87:381\u201393.","journal-title":"Eur J Haematol"},{"key":"85_CR25","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/sj.leu.2402889","volume":"17","author":"N Bubnoff Von","year":"2003","unstructured":"Von Bubnoff N, Peschel C, Duyster J. Resistance of Philadelphia-chromosome positive leukemia towards the kinase inhibitor imatinib (STI571, Glivec): a targeted oncoprotein strikes back. Leukemia. 2003;17:829\u201338.","journal-title":"Leukemia"},{"key":"85_CR26","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1126\/science.1062538","volume":"293","author":"ME Gorre","year":"2001","unstructured":"Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR\u2013ABL gene mutation or amplification. Science. 2001;293:876\u201380.","journal-title":"Science"},{"key":"85_CR27","doi-asserted-by":"crossref","first-page":"400","DOI":"10.4161\/cc.4.3.1560","volume":"4","author":"N Bubnoff von","year":"2005","unstructured":"von Bubnoff N, Barwisch S, Speicher MR, et al. A cell-based screening strategy that predicts mutations in oncogenic tyrosine kinases: implications for clinical resistance in targeted cancer treatment. Cell Cycle. 2005;4:400\u20136.","journal-title":"Cell Cycle"},{"key":"85_CR28","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1182\/blood-2002-09-2896","volume":"102","author":"S Branford","year":"2003","unstructured":"Branford S, Rudzki Z, Walsh S, et al. Detection of BCR\u2013ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (p-loop) are associated with a poor prognosis. Blood. 2003;102:276\u201383.","journal-title":"Blood"},{"key":"85_CR29","doi-asserted-by":"crossref","first-page":"7374","DOI":"10.1158\/1078-0432.CCR-06-1516","volume":"12","author":"S Soverini","year":"2006","unstructured":"Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006;12:7374\u20139.","journal-title":"Clin Cancer Res"},{"key":"85_CR30","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.1200\/JCO.2005.05.531","volume":"23","author":"S Soverini","year":"2005","unstructured":"Soverini S, Martinelli G, Rosti G, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol. 2005;23:4100\u20139.","journal-title":"J Clin Oncol"},{"key":"85_CR31","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1200\/JCO.2011.35.0934","volume":"29","author":"WT Parker","year":"2011","unstructured":"Parker WT, Lawrence RM, Ho M, et al. Sensitive detection of BCR\u2013ABL1 mutations in patients with chronic myeloid leukemia after imatinib resistance is predictive of outcome during subsequent therapy. J Clin Oncol. 2011;29:4250\u20139.","journal-title":"J Clin Oncol"},{"key":"85_CR32","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1182\/blood.V95.5.1758.005a41_1758_1766","volume":"95","author":"P Coutre le","year":"2000","unstructured":"le Coutre P, Tassi E, Varella-Garcia M, et al. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood. 2000;95:1758\u201366.","journal-title":"Blood"},{"key":"85_CR33","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1182\/blood.V96.3.1070","volume":"96","author":"FX Mahon","year":"2000","unstructured":"Mahon FX, Deininger MW, Schultheis B, et al. Selection and characterization of BCR\u2013ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood. 2000;96:1070\u20139.","journal-title":"Blood"},{"key":"85_CR34","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1038\/sj.leu.2402741","volume":"16","author":"A Hochhaus","year":"2002","unstructured":"Hochhaus A, Kreil S, Corbin AS. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia. 2002;16:2190\u20136.","journal-title":"Leukemia"},{"key":"85_CR35","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1038\/sj.leu.2403928","volume":"19","author":"RG Piazza","year":"2005","unstructured":"Piazza RG, Magistroni V, Andreoni F, et al. Imatinib dose increase up to 1200\u00a0mg daily can induce new durable complete cytogenetic remissions in relapsed Ph+ chronic myeloid leukemia patients. Leukemia. 2005;19:1985\u20137.","journal-title":"Leukemia"},{"key":"85_CR36","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1182\/blood-2003-12-4276","volume":"104","author":"J Thomas","year":"2004","unstructured":"Thomas J, Wang L, Clark RE, et al. Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004;104:3739\u201345.","journal-title":"Blood"},{"key":"85_CR37","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/sj.clpt.6100268","volume":"83","author":"J Wang","year":"2008","unstructured":"Wang J, Giannoudis A, Lane S, et al. Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia. Clin Pharmacol Ther. 2008;83:258\u201364.","journal-title":"Clin Pharmacol Ther"},{"key":"85_CR38","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1182\/blood-2007-06-093617","volume":"110","author":"DL White","year":"2007","unstructured":"White DL, Saunders VA, Dang P, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood. 2007;110:4064\u201372.","journal-title":"Blood"},{"key":"85_CR39","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1200\/JCO.2009.26.5819","volume":"28","author":"DL White","year":"2010","unstructured":"White DL, Dang P, Engler J, et al. Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib. J Clin Oncol. 2010;28:2761\u20137.","journal-title":"J Clin Oncol"},{"key":"85_CR40","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1182\/blood.V101.6.2368","volume":"101","author":"FX Mahon","year":"2003","unstructured":"Mahon FX, Belloc F, Lagarde V, et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood. 2003;101:2368\u201373.","journal-title":"Blood"},{"key":"85_CR41","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1182\/blood-2008-03-147744","volume":"112","author":"S Dulucq","year":"2008","unstructured":"Dulucq S, Bouchet S, Turcq B, et al. Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2008;112:2024\u20137.","journal-title":"Blood"},{"key":"85_CR42","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1182\/blood-2007-10-116475","volume":"111","author":"RA Larson","year":"2008","unstructured":"Larson RA, Druker BJ, Guilhot F, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022\u20138.","journal-title":"Blood"},{"key":"85_CR43","doi-asserted-by":"crossref","first-page":"5401","DOI":"10.1182\/blood-2008-12-196543","volume":"113","author":"L Noens","year":"2009","unstructured":"Noens L, van Lierde MA, De Bock R, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113:5401\u201311.","journal-title":"Blood"},{"key":"85_CR44","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1200\/JCO.2009.26.3087","volume":"28","author":"D Marin","year":"2010","unstructured":"Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28:2381\u20138.","journal-title":"J Clin Oncol"},{"key":"85_CR45","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00228-009-0772-y","volume":"66","author":"H Green","year":"2010","unstructured":"Green H, Skoglund K, Rommel F, et al. CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity. Eur J Clin Pharmacol. 2010;66:383\u20136.","journal-title":"Eur J Clin Pharmacol"},{"key":"85_CR46","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/jnci\/92.20.1641","volume":"92","author":"C Gambacorti-Passerini","year":"2000","unstructured":"Gambacorti-Passerini C, Barni R, le Coutre P, et al. Role of alpha 1 acid glycoprotein in the vivo resistance of human BCR\u2013ABL(+) leukemic cells to the abl inhibitor STI571. J Natl Cancer Inst. 2000;92:1641\u201350.","journal-title":"J Natl Cancer Inst"},{"key":"85_CR47","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1158\/1078-0432.CCR-05-2596","volume":"12","author":"C Debaldo","year":"2006","unstructured":"Debaldo C, Chatelut E, Re M, et al. Pharmacokinetic\u2013pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res. 2006;12:6073\u20138.","journal-title":"Clin Cancer Res"},{"key":"85_CR48","first-page":"625","volume":"9","author":"C Gambacorti-Passerini","year":"2003","unstructured":"Gambacorti-Passerini C, Zucchetti M, Russo D, et al. Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients. Clin Cancer Res. 2003;9:625\u201332.","journal-title":"Clin Cancer Res"},{"key":"85_CR49","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1182\/blood.V94.6.2056","volume":"94","author":"T Holyoake","year":"1999","unstructured":"Holyoake T, Jiang X, Eaves C, et al. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood. 1999;94:2056\u201364.","journal-title":"Blood"},{"key":"85_CR50","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1056\/NEJMoa040258","volume":"351","author":"CH Jamieson","year":"2004","unstructured":"Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351:657\u201367.","journal-title":"N Engl J Med"},{"key":"85_CR51","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1073\/pnas.0900189106","volume":"106","author":"AE Abrahamsson","year":"2009","unstructured":"Abrahamsson AE, Geron J, Gotlib J, et al. Glycogen synthase kinase 3B missplicing contributes to leukemia stem cell generation. Proc Natl Acad Sci. 2009;106:3925\u20139.","journal-title":"Proc Natl Acad Sci"},{"key":"85_CR52","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nature08734","volume":"463","author":"K Naka","year":"2010","unstructured":"Naka K, Hoshii T, Muraguchi T, et al. TGF\u2013bgr\u2013FOXO signalling maintains leukemia-initiating cells in chronic myeloid leukemia. Nature. 2010;463:676\u201380.","journal-title":"Nature"},{"key":"85_CR53","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature07737","volume":"458","author":"C Zhao","year":"2009","unstructured":"Zhao C, Chen A, Jamieson CH, et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukemia. Nature. 2009;458:776\u20139.","journal-title":"Nature"},{"key":"85_CR54","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1182\/blood-2009-10-248211","volume":"117","author":"W Warsch","year":"2011","unstructured":"Warsch W, Kollmann K, Eckelhart E, et al. High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia. Blood. 2011;117:3409\u201320.","journal-title":"Blood"},{"key":"85_CR55","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1182\/blood-2008-03-144790","volume":"113","author":"A Quintas-Cardama","year":"2009","unstructured":"Quintas-Cardama A, Cortes J. Molecular biology of bcr\u2013abl1-positive chronic myeloid leukemia. Blood. 2009;113:1619\u201330.","journal-title":"Blood"},{"key":"85_CR56","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/ng1343","volume":"36","author":"Y Hu","year":"2004","unstructured":"Hu Y, Liu Y, Pelletier S, et al. Requirement of Src kinases Lyn, Hck and Fgr for BCR\u2013ABL1 induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet. 2004;36:453\u201361.","journal-title":"Nat Genet"},{"key":"85_CR57","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1158\/1535-7163.MCT-09-0168","volume":"8","author":"S Gross","year":"2009","unstructured":"Gross S, Puissant A, Dufies M, et al. Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR\u2013ABL inhibitors. Mol Cancer Ther. 2009;8:1924\u201333.","journal-title":"Mol Cancer Ther"},{"key":"85_CR58","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/jnci\/djn188","volume":"100","author":"J Wu","year":"2008","unstructured":"Wu J, Meng F, Kong LY, et al. Association between imatinib-resistant BCR\u2013ABL mutation-negative leukemia and persistent activation of LYN kinase. J Natl Cancer Inst. 2008;100:926\u201339.","journal-title":"J Natl Cancer Inst"},{"key":"85_CR59","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1182\/blood-2002-05-1451","volume":"101","author":"HM Kantarjian","year":"2003","unstructured":"Kantarjian HM, Talpaz M, O\u2019Brien S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003;101:473\u20135.","journal-title":"Blood"},{"key":"85_CR60","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1182\/blood-2003-06-2042","volume":"102","author":"D Marin","year":"2003","unstructured":"Marin D, Goldman JM, Olavarria E, et al. Transient benefit only from increasing the imatinib dose in CML patients who do not achieve complete cytogenetic remissions on conventional doses. Blood. 2003;102:2702\u20133.","journal-title":"Blood"},{"key":"85_CR61","first-page":"2092","volume":"9","author":"JA Zonder","year":"2003","unstructured":"Zonder JA, Pemberton P, Brandt H, et al. The effect of dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to initial treatment. Clin Cancer Res. 2003;9:2092\u20137.","journal-title":"Clin Cancer Res"},{"key":"85_CR62","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/cncr.24066","volume":"115","author":"HM Kantarjian","year":"2009","unstructured":"Kantarjian HM, Larson RA, Guilhot F, et al. Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase. Cancer. 2009;115:551\u201360.","journal-title":"Cancer"},{"key":"85_CR63","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1182\/blood-2008-04-154344","volume":"113","author":"E Jabbour","year":"2009","unstructured":"Jabbour E, Kantarjian HM, Jones D, et al. Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard dose imatinib therapy. Blood. 2009;113:2154\u201360.","journal-title":"Blood"},{"key":"85_CR64","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1038\/leu.2009.32","volume":"23","author":"D Rea","year":"2009","unstructured":"Rea D, Etienne G, Corm S, et al. Imatinib dose escalation for chronic phase-chronic myelogenous leukemia patients in primary suboptimal response to imatinib 400 mg daily standard therapy. Leukemia. 2009;23:1193\u20136.","journal-title":"Leukemia"},{"key":"85_CR65","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/ajh.21680","volume":"85","author":"M Breccia","year":"2010","unstructured":"Breccia M, Stagno F, Vigneri P, et al. Imatinib dose escalation in 74 failure or suboptimal response chronic myeloid leukemia patients at 3-year follow up. Am J Hematol. 2010;85:375\u20137.","journal-title":"Am J Hematol"},{"key":"85_CR66","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3324\/haematol.2009.011452","volume":"95","author":"NP Shah","year":"2010","unstructured":"Shah NP, Kim DW, Kantarjian H, et al. Potent, transient inhibition of BCR\u2013ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica. 2010;95:232\u201340.","journal-title":"Haematologica"},{"issue":"Suppl 1","key":"85_CR67","first-page":"199","volume":"97","author":"D Rea","year":"2012","unstructured":"Rea D, Vellenga E, JunghanB C, et al. Six-year follow-up of patients with imatinib-resistant or imatinib-intolerant chronic-phase chronic myeloid leukemia (CP-CML) receiving dasatinib. Haematologica. 2012;97(Suppl 1):199.","journal-title":"Haematologica"},{"key":"85_CR68","doi-asserted-by":"crossref","first-page":"4944","DOI":"10.1182\/blood-2009-04-214221","volume":"114","author":"MC Muller","year":"2009","unstructured":"Muller MC, Cortes JE, Kim DW, et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to pre-existing BCR\u2013ABL mutations. Blood. 2009;114:4944\u201353.","journal-title":"Blood"},{"key":"85_CR69","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/leu.2013.69","volume":"27","author":"FJ Giles","year":"2013","unstructured":"Giles FJ, le Coutre PD, Pinilla-Ibarz J, et al. Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia. 2013;27:107\u201312.","journal-title":"Leukemia"},{"key":"85_CR70","doi-asserted-by":"crossref","first-page":"4204","DOI":"10.1200\/JCO.2009.21.8230","volume":"27","author":"T Hughes","year":"2009","unstructured":"Hughes T, Saglio G, Branford S, et al. Impact of baseline BCR\u2013ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol. 2009;27:4204\u201310.","journal-title":"J Clin Oncol"},{"key":"85_CR71","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1182\/blood.V112.11.3233.3233","volume":"112","author":"JH Lipton","year":"2008","unstructured":"Lipton JH, le Coutre PD, Wang J, et al. Nilotinib in elderly chronic myeloid leukemia patients in chronic phase (CML-CP) with imatinib resistance or intolerance: efficacy and safety analysis. Blood. 2008;112:3233.","journal-title":"Blood"},{"key":"85_CR72","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1182\/blood.V114.22.3286.3286","volume":"114","author":"PD Coutre le","year":"2009","unstructured":"le Coutre PD, Turkina A, Kim DW, et al. Efficacy and safety of nilotinib in elderly patients with imatinib-resistant or intolerant chronic myeloid leukemia (VML) in chronic phase: a subanalysis of the ENACT (Expanding nilotinib access in clinical trials) study. Blood. 2009;114:3286.","journal-title":"Blood"},{"key":"85_CR73","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.leukres.2011.05.015","volume":"35","author":"R Latagliata","year":"2011","unstructured":"Latagliata R, Breccia M, Castagnetti F, et al. Dasatinib is safe and effective in unselected chronic myeloid leukemia elderly patients resistant\/intolerant to imatinib. Leuk Res. 2011;35:1164\u20139.","journal-title":"Leuk Res"},{"issue":"Suppl 1","key":"85_CR74","first-page":"757","volume":"97","author":"C Gambacorti-Passerini","year":"2012","unstructured":"Gambacorti-Passerini C, Brummendorf T, Cortes J, et al. Efficacy and safety of bosutinib for Philadelphia chromosome-positive leukemia in older versus younger patients. Haematologica. 2012;97(Suppl 1):757.","journal-title":"Haematologica"},{"key":"85_CR75","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1056\/NEJMoa1205127","volume":"367","author":"JE Cortes","year":"2012","unstructured":"Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367:2075\u201388.","journal-title":"N Engl J Med"},{"key":"85_CR76","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1182\/blood.V120.21.163.163","volume":"120","author":"JE Cortes","year":"2012","unstructured":"Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A pivotal phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant or intolerant to dasatinib or nilotinib, or with the T315I BCR\u2013ABL mutation: 12-month follow-up of the PACE trial. Blood. 2012;120:163.","journal-title":"Blood"},{"key":"85_CR77","first-page":"422","volume":"96","author":"N Nanda","year":"2011","unstructured":"Nanda N, Cortes J, Lipton J, et al. Treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients who harbor the BCR\u2013ABL T315I mutation with subcutaneous omacetaxine results in improved survival compared to historical data. Haematologica. 2011;96:422\u20133.","journal-title":"Haematologica"},{"key":"85_CR78","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1182\/blood.V114.22.861.861","volume":"114","author":"J Cortes","year":"2009","unstructured":"Cortes J, Raghunadharao D, Parikh P, et al. Safety and efficacy of subcutaneous-administered omacetaxine mepesuccinate in chronic myeloid leukemia (CML) patients who are resistant or intolerant to two or more tyrosine kinase inhibitors-results of a multicenter phase 2\/3 study. Blood. 2009;114:861.","journal-title":"Blood"},{"key":"85_CR79","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1182\/blood-2012-03-415307","volume":"120","author":"J Cortes","year":"2012","unstructured":"Cortes J, Lipton JH, Rea D, et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012;120:2573\u201380.","journal-title":"Blood"},{"key":"85_CR80","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1182\/blood-2012-02-409763","volume":"119","author":"E Warlick","year":"2012","unstructured":"Warlick E, Ahn KW, Pedersen TL, et al. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood. 2012;119:4083\u201390.","journal-title":"Blood"},{"key":"85_CR81","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1182\/blood.V116.21.3421.3421","volume":"116","author":"HJ Khoury","year":"2010","unstructured":"Khoury HJ, Cortes JE, Kantarjian HM, et al. Safety and efficacy of dasatinib (DAS) vs imatinib (IM) by baseline comorbidity in patients with chronic myeloid leukemia in chronic phase (CML-CP): analysis of the DASISION trial. Blood. 2010;116:3421.","journal-title":"Blood"},{"key":"85_CR82","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1182\/blood-2011-08-376087","volume":"119","author":"HM Kantarjian","year":"2012","unstructured":"Kantarjian HM, Shah NP, Cortes JP, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119:1123\u20139.","journal-title":"Blood"},{"key":"85_CR83","doi-asserted-by":"crossref","first-page":"3768","DOI":"10.1182\/blood.V118.21.3768.3768","volume":"114","author":"RA Larson","year":"2011","unstructured":"Larson RA, Bunworasate U, Turkina AG, et al. Nilotinib shows safety and efficacy in older patients (<65 years) with newly diagnosed chronic myeloid leukemia in chronic phase comparable with that in younger patients with chronic myeloid leukemia in chronic phase: results from ENESTnd. Blood. 2011;114:3768.","journal-title":"Blood"},{"key":"85_CR84","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1182\/blood.V120.21.1676.1676","volume":"120","author":"H Kantarjian","year":"2012","unstructured":"Kantarjian H, Kim DW, Issagrisil S, et al. ENESTnd 4-year update: continued superiority of nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP). Blood. 2012;120:1676.","journal-title":"Blood"},{"key":"85_CR85","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1038\/leu.2012.134","volume":"26","author":"RA Larson","year":"2012","unstructured":"Larson RA, Hochhaus A, Hughes TP, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia. 2012;26:2197\u2013203.","journal-title":"Leukemia"},{"key":"85_CR86","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.leukres.2012.03.010","volume":"36","author":"M Breccia","year":"2012","unstructured":"Breccia M, Efficace F, Alimena G. Progressive arterial occlusive disease (PAOD) and pulmonary arterial hypertension (PAH) as new adverse events of second generation TKIs in CML treatment: who\u2019s afraid of the big bad wolf? Leuk Res. 2012;36:813\u20134.","journal-title":"Leuk Res"},{"key":"85_CR87","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/jnci\/djr292","volume":"103","author":"P Coutre le","year":"2011","unstructured":"le Coutre P, Rea D, Abruzzese E, et al. Severe peripheral arterial disease during nilotinib therapy. J Natl Cancer Inst. 2011;103:1347\u20138.","journal-title":"J Natl Cancer Inst"},{"key":"85_CR88","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1182\/blood-2011-12-398156","volume":"120","author":"M Schwarz","year":"2012","unstructured":"Schwarz M, Kim TD, Mirault T, et al. Elevated risk of peripheral artery occlusive disease (PAOD) in nilotinib treated chronic phase chronic myeloid leukemia (CML) patients assessed by ankle-brachial index (ABI) and duplex ultrasonography. Blood. 2012;120:914.","journal-title":"Blood"},{"key":"85_CR89","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1200\/JCO.2011.38.7522","volume":"30","author":"JE Cortes","year":"2012","unstructured":"Cortes JE, Kim DW, Kantarjian HM, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol. 2012;30:3486\u201392.","journal-title":"J Clin Oncol"},{"key":"85_CR90","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1182\/blood.V120.21.4442.4442","volume":"120","author":"C Gambacorti-Passerini","year":"2012","unstructured":"Gambacorti-Passerini C, Brummendorf TH, Kim DW, et al. Efficacy and tolerability of bosutinib and imatinib in older versus younger patients with newly diagnosed chronic phase chronic myeloid leukemia-BELA trial. Blood. 2012;120:4442.","journal-title":"Blood"}],"container-title":["Drugs &amp; Aging"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40266-013-0085-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40266-013-0085-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40266-013-0085-9","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T22:34:27Z","timestamp":1715294067000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40266-013-0085-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,25]]},"references-count":90,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["85"],"URL":"https:\/\/doi.org\/10.1007\/s40266-013-0085-9","relation":{},"ISSN":["1170-229X","1179-1969"],"issn-type":[{"value":"1170-229X","type":"print"},{"value":"1179-1969","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,25]]}}}