{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:15:25Z","timestamp":1789964125960,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T00:00:00Z","timestamp":1564185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T00:00:00Z","timestamp":1564185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To assess the incidence of BCR\u2010ABL kinase domain (KD) mutation detection and its prognostic significance in chronic phase chronic myeloid leukemia (CP\u2010CML) patients treated with tyrosine kinase inhibitors (TKIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>We analyzed characteristics and outcome of 253 CP\u2010CML patients who had at least one mutation analysis performed using direct sequencing. Of them, 187 patients were early CP (ECP) and 66 were late CP late chronic phase (LCP) and 88% were treated with Imatinib as first\u2010line TKI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 80 (32%) patients harbored BCR\u2010ABL KD mutations. A BCR\u2010ABL KD mutation was identified in 57% of patients, who progressed to accelerated or blastic phases (AP\u2010BP), and 47%, 29%, 35%, 16% and 26% in patients in CP\u2010CML at the time of mutation analysis who lost a complete hematologic response, failed to achieve or loss of a prior complete cytogenetic and major molecular response, respectively.<\/jats:p>\n                    <jats:p>\n                      Overall survival and cumulative incidence of CML\u2010related death were significantly correlated with the disease phase whatever the absence or presence of a mutation was and for the latter the mutation subgroup (T315I vs P\u2010loop vs non\u2010T315I non\u2010P\u2010loop) (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;.001). Considering patients who were in CP at the time of mutation analysis, LCP mutated patients had a significantly worse outcome than ECP\u2010mutated patients despite a lower incidence of T315I and P\u2010loop mutations (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;.001). With a median follow\u2010up from mutation analysis to last follow\u2010up of 5\u00a0years, T315I and P\u2010loop mutations were not associated with a worse outcome in ECP patients (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\u00a0.817).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that early mutation detection together with accessibility to 2nd and 3rd generation TKIs have reversed the worst outcome associated with BCR\u2010ABL KD mutations whatever the mutation subgroup in CP\u2010CML patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.2410","type":"journal-article","created":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T04:40:09Z","timestamp":1564202409000},"page":"5173-5182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Incidence and outcome of BCR\u2010ABL mutated chronic myeloid leukemia patients who failed to tyrosine kinase inhibitors"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7600-4954","authenticated-orcid":false,"given":"Gabriel","family":"Etienne","sequence":"first","affiliation":[{"name":"D\u00e9partement d'H\u00e9matologie Institut Bergoni\u00e9 Bordeaux France"},{"name":"Laboratory of Mammary and Leukaemic Oncogenesis INSERM U1218, Universit\u00e9 de Bordeaux Bordeaux France"},{"name":"Groupe Fi\u2010LMC, H\u00f4pital Haut\u2010L\u00e9v\u00eaque Pessac 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H\u00f4pital Haut L\u00e9v\u00eaque CHU de Bordeaux Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Hayette","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Pierre","family":"Fort","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'H\u00e9matologie Institut Bergoni\u00e9 Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Sujobert","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Centre Hospitalier Lyon Sud Pierre B\u00e9nite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fontanet","family":"Bijou","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'H\u00e9matologie Institut Bergoni\u00e9 Bordeaux 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