{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:14:19Z","timestamp":1789013659686,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A reduction in BCR-ABL1\/ABL1IS transcript levels to &lt;10% after 3 months or &lt;1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1\/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (\u2265 MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1\/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with BCR-ABL1\/ABL1IS values &gt;10% at 3 months but &lt;1% at 6 months fared significantly better than individuals with BCR-ABL1\/ABL1IS &lt;10% at 3 months but &gt;1% at 6 months (event-free survival 68.2% vs. 32.7%; p &lt; 0.001). Likewise, subjects with BCR-ABL1\/ABL1IS at 3 months &gt;10% but &lt;1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1\/ABL1IS &lt;10% at 3 months but &gt;1% at 6 months (75% vs. 18.2%; p &lt; 0.001). Finally, lower BCR-ABL1\/GUSIS transcripts at diagnosis were associated with BCR-ABL1\/ABL1IS values &lt;1% at 6 months (p &lt; 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1\/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.<\/jats:p>","DOI":"10.3390\/ijms20092226","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:19:59Z","timestamp":1557389999000},"page":"2226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib"],"prefix":"10.3390","volume":"20","author":[{"given":"Stefania","family":"Stella","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Zammit","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplant, AOU Policlinico - V. Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Rita","family":"Vitale","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Stella","family":"Pennisi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Massimino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8012-5134","authenticated-orcid":false,"given":"Elena","family":"Tirr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5746-7451","authenticated-orcid":false,"given":"Stefano","family":"Forte","sequence":"additional","affiliation":[{"name":"Mediterranean Institute of Oncology, 95029 Viagrande, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Spitaleri","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplant, AOU Policlinico - V. Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostino","family":"Antolino","sequence":"additional","affiliation":[{"name":"Department of Transfusional Medicine, Maria Patern\u00f2-Arezzo Hospital, 97100 Ragusa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Division of Hematology, A.O.U. Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Accurso","sequence":"additional","affiliation":[{"name":"Division of Hematology, A.O.U. Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donato","family":"Mannina","sequence":"additional","affiliation":[{"name":"Division of Hematology, Papardo Hospital, 98158 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefana","family":"Impera","sequence":"additional","affiliation":[{"name":"Division of Oncology and Hematology, ARNAS Garibaldi-Nesima, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Musolino","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Russo","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Malato","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplant, Villa Sofia-Cervello Hospital, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mineo","sequence":"additional","affiliation":[{"name":"Division of Hematology, San Vincenzo Hospital, 98039 Taormina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Musso","sequence":"additional","affiliation":[{"name":"Division of Hematology, La Maddalena Hospital, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Porretto","sequence":"additional","affiliation":[{"name":"Division of Hematology, La Maddalena Hospital, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Martino","sequence":"additional","affiliation":[{"name":"Hematology Department, Grande Ospedale Metropolitano, Reggio Calabria, 89124 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Raimondo","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplant, AOU Policlinico - V. Emanuele, 95123 Catania, Italy"},{"name":"Department of Surgery, Medical and Surgical Specialities, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Manzella","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Vigneri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-158X","authenticated-orcid":false,"given":"Fabio","family":"Stagno","sequence":"additional","affiliation":[{"name":"Division of Hematology and Bone Marrow Transplant, AOU Policlinico - V. Emanuele, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1586\/14737140.2016.1151356","article-title":"Imatinib mesylate in chronic myeloid leukemia: Frontline treatment and long-term outcomes","volume":"16","author":"Stagno","year":"2016","journal-title":"Expert Rev. 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