{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:32:26Z","timestamp":1791307946814,"version":"4.3.1"},"reference-count":105,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T00:00:00Z","timestamp":1453420800000},"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":[[2016,2]]},"abstract":"<jats:p><jats:bold><jats:italic>Disease overview:<\/jats:italic><\/jats:bold> Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1\u20102 cases per 100,000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. <jats:bold><jats:italic>Diagnosis<\/jats:italic>:<\/jats:bold> CML is characterized by a balanced genetic translocation, <jats:italic>t<\/jats:italic>(9;22)(q34;q11.2), involving a fusion of the Abelson gene (<jats:italic>ABL1<\/jats:italic>) from chromosome 9q34 with the breakpoint cluster region (<jats:italic>BCR<\/jats:italic>) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a <jats:italic>BCR\u2010ABL1<\/jats:italic> fusion oncogene, which in turn translates into a BCR\u2010ABL oncoprotein. <jats:bold><jats:italic>Frontline therapy<\/jats:italic>:<\/jats:bold> Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib are approved by the United States Food and Drug Administration for first\u2010line treatment of patients with newly diagnosed CML in chronic phase (CML\u2010CP). Clinical trials with 2nd generation TKIs reported significantly deeper and faster responses; their impact on long\u2010term survival remains to be determined. <jats:bold><jats:italic>Salvage therapy<\/jats:italic>:<\/jats:bold> For patients who fail frontline therapy, second\u2010line options include second and third generation TKIs. Although second and third generation TKIs are potent and selective TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients\u2019 comorbidities, disease stage, and BCR\u2010ABL1 mutational status. Patients who develop the T315I \u201cgatekeeper\u201d mutation display resistance to all currently available TKIs except ponatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML\u2010CP who have failed at least two TKIs, and for all patients in advanced phase disease. Am. J. Hematol. 91:253\u2013265, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24275","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T14:29:34Z","timestamp":1453472974000},"page":"252-265","source":"Crossref","is-referenced-by-count":154,"title":["Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring"],"prefix":"10.1002","volume":"91","author":[{"given":"Elias","family":"Jabbour","sequence":"first","affiliation":[{"name":"Department of Leukemia the University of Texas M. D. Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[{"name":"Department of Leukemia the University of Texas M. D. Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,22]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Cancer Facts & Figures 2015","author":"American Cancer Society","year":"2015"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26679"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.6.1838.1838"},{"key":"e_1_2_12_6_1","first-page":"1111","article-title":"Factor independence of human myeloid leukemia cell lines is associated with increased phosphorylation of the proto\u2010oncogene Raf\u20101","volume":"22","author":"Okuda K","year":"1994","journal-title":"Exp Hematol"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.25.11746"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90241-4"},{"key":"e_1_2_12_9_1","first-page":"247","article-title":"Constitutive activation of STAT5 by the BCR\u2010ABL oncogene in chronic myelogenous leukemia","volume":"13","author":"Shuai K","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.3.811"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.49.31704"},{"key":"e_1_2_12_12_1","first-page":"1517","article-title":"An evidence\u2010based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: Developed for the American Society of Hematology","volume":"94","author":"Silver RT","year":"1999","journal-title":"Blood"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V114.22.1126.1126","article-title":"International randomized study of interferon vs. STI571 (IRIS) 8\u2010year follow up: Sustained survival and low risk for progression of events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML\u2010CP) treated with imatinib","volume":"114","author":"Deininger M","year":"2009","journal-title":"Blood"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23427"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-110189"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402329"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9083"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022457"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.3724"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1004095"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm049486a"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0259"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4187"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099480"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002315"},{"key":"e_1_2_12_26_1","first-page":"152","article-title":"Final study results of the Phase 3 dasatinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase (CML\u2010CP) trial (DASISION, CA180\u2010056)","volume":"124","author":"Cortes J","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-410688"},{"key":"e_1_2_12_28_1","first-page":"517","article-title":"Spirit 2: An NCRI randomized study comparing dasatinib with imatinib in patients with newly diagnosed CML","volume":"124","author":"O'Brien SG","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.01.007"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912614"},{"key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"7073","DOI":"10.1200\/jco.2014.32.15_suppl.7073","article-title":"ENESTnd 5\u2010year (y) update: Long\u2010term outcomes of patients (pts) with chronic myeloid leukemia in chronic phase (CML\u2010CP) treated with frontline nilotinib (NIL) versus imatinib (IM)","volume":"32","author":"Larson RA","year":"2014","journal-title":"J Clin Oncol (Meeting Abstracts)"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-601674"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00021-6"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2013.0157"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.079921"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-180604"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24257"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22037"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2012.04.005"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22051"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.69"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsb1013826"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.49.1845"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-490003"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djr060"},{"key":"e_1_2_12_46_1","first-page":"738","article-title":"What is the most cost\u2010effective strategy for treating newly diagnosed chronic myeloid leukemia (cml) after imatinib loses patent exclusivity?","volume":"124","author":"Larson RA","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971-5851.123716"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V63.4.789.789"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.11.850"},{"key":"e_1_2_12_50_1","article-title":"Impact of BCR\u2010ABL transcript type on response and survival in patients with chronic phase chronic myeloid leukemia (CML\u2010CP) treated with tyrosine kinase inhibitors (TKI)","volume":"126","author":"Jain P","year":"2015","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-501569"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-229864"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.9176"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.0598"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.6999"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.6565"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-490128"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-466037"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.090282"},{"key":"e_1_2_12_60_1","first-page":"254","article-title":"Any BRC\u2010ABL reduction below 10% at 6 months of therapy significantly improves outcome for CML patients with a poor response at 3 months","volume":"122","author":"Branford S","year":"2013","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.0693"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-566323"},{"key":"e_1_2_12_63_1","first-page":"95","article-title":"Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with suboptimal cytogenetic response on imatinib: First results of the LASOR trial","volume":"122","author":"Cortes JE","year":"2013","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_64_1","first-page":"94","article-title":"Achievement and maintenance of deeper molecular response by switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with residual disease on long\u2010term imatinib: Enestcmr 36\u2010month follow up","volume":"122","author":"Leber B","year":"2013","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.3087"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200725060-00004"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-196543"},{"key":"e_1_2_12_68_1","unstructured":"Bristol\u2010Myers Squibb Company. Sprycel\u00ae(dasatinib) prescribing information. Princeton NJ 2011."},{"key":"e_1_2_12_69_1","unstructured":"Novartis Pharmaceuticals Corporation. Tasigna\u00ae (nilotinib) prescribing information. East Hanover NJ 2011."},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-154344"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24504"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V118.21.3780.3780"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V118.21.2765.2765"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-355594"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V118.21.451.451"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24325"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.09.028"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2010.01054.x"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306494"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.3135.3135"},{"key":"e_1_2_12_81_1","unstructured":"Iclusig (ponatinib) [prescribing information]. Cambridge MA: ARIAD Pharmaceuticals Inc;2014."},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-080838"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25717"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-214221"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.21.8230"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-513937"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2012.12.005"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-302679"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-141689"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2008.90"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2014-0218"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"e_1_2_12_93_1","first-page":"255","article-title":"Long term follow\u2010up after imatinib cessation for patients in deep molecular response: The updated results of the STIM1 study","volume":"122","author":"Mahon FX","year":"2013","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-483750"},{"key":"e_1_2_12_95_1","first-page":"654","article-title":"Preliminary report of the STIM2 study: A multicenter stop imatinib trial for chronic phase chronic myeloid leukemia de novo patients on imatinib","volume":"122","author":"Mahon FX","year":"2013","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.5797"},{"key":"e_1_2_12_97_1","first-page":"151","article-title":"Interim analysis of a pan European Stop Tyrosine Kinase Inhibitor Trial in chronic myeloid leukemia: The EURO\u2010SKI study","volume":"124","author":"Mahon F","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.3339"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-031682"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-019836"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22778"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.323"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2958"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-261586"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190601075973"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2013.08.008"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.24275","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.24275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T12:42:55Z","timestamp":1695472975000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.24275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,22]]},"references-count":105,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1002\/ajh.24275"],"URL":"https:\/\/doi.org\/10.1002\/ajh.24275","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,22]]}}}