{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T18:38:51Z","timestamp":1768415931895,"version":"3.49.0"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"4","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_almed-2024-0069_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      <jats:italic>BCR-ABL<\/jats:italic>\n                      kinase domain mutations are an important cause of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) of which T315I is the most treatment-resilient. This study aimed to observe the frequency of T315I and its impact on disease prognosis in terms of progression and survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_almed-2024-0069_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with a response which categorized them into warning zone\/or who failed to respond to their TKI treatment completely as per the European LeukemiaNet (ELN) were labeled as non-responders. They were assessed for T315I mutation using amplification refractory mutation system-polymerase chain reaction  (ARMS-PCR) and validated via sequencing. Patients were then longitudinally followed for 96\u00a0months for the prognostic impact of the mutation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_almed-2024-0069_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 102 non-responders, T315I mutation was detected in 21.6\u202f% of patients with a female preponderance. Almost 59\u202f% of mutation-harbouring patients were labelled as low Sokal risk at baseline. The disease progression into the blastic phase was reported in 58.8\u202f% of mutation-harbouring patients. Overall survival (study period: 96\u00a0months) was 81.8\u202f% in patients harbouring T315I mutation. Patients in the blastic phase had significant odds of harbouring T315I mutation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_almed-2024-0069_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sub-optimal response or failure to TKI treatment indicates the development of resistance due to the presence of T315I mutation or other mutation(s). Early identification will help redirect the patient\u2019s treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/almed-2024-0069","type":"journal-article","created":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T05:20:29Z","timestamp":1726377629000},"page":"412-417","source":"Crossref","is-referenced-by-count":2,"title":["T315I\u00a0\u2013 a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia"],"prefix":"10.1515","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-0672","authenticated-orcid":false,"given":"Bushra","family":"Kaleem","sequence":"first","affiliation":[{"name":"Department of Clinical Research , National Institute of Blood Disease and Bone Marrow Transplantation , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadaf","family":"Shahab","sequence":"additional","affiliation":[{"name":"Department of Clinical Research , National Institute of Blood Disease and Bone Marrow Transplantation , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahir Sultan","family":"Shamsi","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology , National Institute of Blood Disease and Bone Marrow Transplantation , Karachi , Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"2025121815520082383_j_almed-2024-0069_ref_001","doi-asserted-by":"crossref","unstructured":"Melo, JV, Hughes, TP, Apperley, JF. Chronic myeloid leukemia. Hematology Am Soc Hematol Educ Program 2003;2003:132\u201352. https:\/\/doi.org\/10.1182\/asheducation-2003.1.132.","DOI":"10.1182\/asheducation-2003.1.132"},{"key":"2025121815520082383_j_almed-2024-0069_ref_002","doi-asserted-by":"crossref","unstructured":"Hochhaus, A, Larson, RA, Guilhot, F, Radich, JP, Branford, S, Hughes, TP, et al.. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med 2017;376:917\u201327. https:\/\/doi.org\/10.1056\/NEJMoa1609324.","DOI":"10.1056\/NEJMoa1609324"},{"key":"2025121815520082383_j_almed-2024-0069_ref_003","doi-asserted-by":"crossref","unstructured":"Apperley, JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 2007;8:1018\u201329. https:\/\/doi.org\/10.1016\/S1470-2045(07)70342-X.","DOI":"10.1016\/S1470-2045(07)70342-X"},{"key":"2025121815520082383_j_almed-2024-0069_ref_004","doi-asserted-by":"crossref","unstructured":"Jabbour, E, Branford, S, Saglio, G, Jones, D, Cortes, JE, Kantarjian, HM. Practical advice for determining the role of BCR-ABL mutations in guiding tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer 2011;117:1800\u201311. https:\/\/doi.org\/10.1002\/cncr.25717.","DOI":"10.1002\/cncr.25717"},{"key":"2025121815520082383_j_almed-2024-0069_ref_005","doi-asserted-by":"crossref","unstructured":"Kantarjian, H, Giles, F, Wunderle, L, Bhalla, K, O\u2019Brien, S, Wassmann, B, et al.. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006;354:2542\u201351. https:\/\/doi.org\/10.1056\/NEJMoa055104.","DOI":"10.1056\/NEJMoa055104"},{"key":"2025121815520082383_j_almed-2024-0069_ref_006","doi-asserted-by":"crossref","unstructured":"Branford, S, Melo, JV, Hughes, TP. Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter? Blood 2009;114:5426\u201335. https:\/\/doi.org\/10.1182\/blood-2009-08-215939.","DOI":"10.1182\/blood-2009-08-215939"},{"key":"2025121815520082383_j_almed-2024-0069_ref_007","doi-asserted-by":"crossref","unstructured":"Nicolini, FE, Mauro, MJ, Martinelli, G, Kim, DW, Soverini, S, Muller, MC, et al.. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood 2009;114:5271\u20138. https:\/\/doi.org\/10.1182\/blood-2009-04-219410.","DOI":"10.1182\/blood-2009-04-219410"},{"key":"2025121815520082383_j_almed-2024-0069_ref_008","doi-asserted-by":"crossref","unstructured":"Baccarani, M, Castagnetti, F, Gugliotta, G, Rosti, G. A review of the European LeukemiaNet recommendations for the management of CML. Ann Hematol 2015;94(Suppl 2):S141\u20137. https:\/\/doi.org\/10.1007\/s00277-015-2322-2.","DOI":"10.1007\/s00277-015-2322-2"},{"key":"2025121815520082383_j_almed-2024-0069_ref_009","unstructured":"Kang, HY, Hwang, JY, Kim, SH, Goh, HG, Kim, M, Kim, DW. Comparison of allele specific oligonucleotide-polymerase chain reaction and direct sequencing for high throughput screening of ABL kinase domain mutations in chronic myeloid leukemia resistant to imatinib. Haematologica 2006;91:659\u201362. https:\/\/doi.org\/10.3324\/%25x."},{"key":"2025121815520082383_j_almed-2024-0069_ref_010","doi-asserted-by":"crossref","unstructured":"Jabbour, E, Kantarjian, HM, Jones, D, Shan, J, O\u2019Brien, S, Reddy, N, 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. https:\/\/doi.org\/10.1182\/blood-2008-04-154344.","DOI":"10.1182\/blood-2008-04-154344"},{"key":"2025121815520082383_j_almed-2024-0069_ref_011","doi-asserted-by":"crossref","unstructured":"Larson, RA, Kim, DW, Issaragrilsil, S, le Coutre, P, Llacer, PED, Etienne, G, et al.. Efficacy and safety of nilotinib (NIL) vs imatinib (IM) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): long-term follow-up (f\/u) of ENESTnd. Blood 2014;124:4541. https:\/\/doi.org\/10.1182\/blood.V124.21.4541.4541.","DOI":"10.1182\/blood.V124.21.4541.4541"},{"key":"2025121815520082383_j_almed-2024-0069_ref_012","unstructured":"Hughes, T, Coutre, P, Jootar, S, Reiffers, J, Turkina, A, Saglio, G, et al.. ENESTnd 5-year follow-up: continued benefit of frontline nilotinib (NIL) compared with imatinib (IM) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP). Haematologica 2014;99(S1):236\u20137."},{"key":"2025121815520082383_j_almed-2024-0069_ref_013","doi-asserted-by":"crossref","unstructured":"Branford, S, Hughes, T. Detection of BCR-ABL mutations and resistance to imatinib mesylate. Methods Mol Med 2006;125:93\u2013106. https:\/\/doi.org\/10.1385\/1-59745-017-0:93.","DOI":"10.1385\/1-59745-017-0:93"},{"key":"2025121815520082383_j_almed-2024-0069_ref_014","doi-asserted-by":"crossref","unstructured":"Jabbour, E, Kantarjian, H, Jones, D, Talpaz, M, Bekele, N, O\u2019Brien, S, et al.. 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Leuk Lymphoma 2010;51:1072\u20138. https:\/\/doi.org\/10.3109\/10428191003729741.","DOI":"10.3109\/10428191003729741"},{"key":"2025121815520082383_j_almed-2024-0069_ref_017","doi-asserted-by":"crossref","unstructured":"Srivastava, S, Dutt, S. Imatinib mesylate resistance and mutations: an Indian experience. Indian J Med Paediatr Oncol 2013;34:213\u201320. https:\/\/doi.org\/10.4103\/0971-5851.123748.","DOI":"10.4103\/0971-5851.123748"},{"key":"2025121815520082383_j_almed-2024-0069_ref_018","doi-asserted-by":"crossref","unstructured":"Ahn, JS, Kim, YK, Lee, SR, Yu, L, Yang, DH, Cho, SH, et al.. Coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second-generation tyrosine kinase inhibitors predict the discrepancy of in\u00a0vitro drug sensitivity. Cancer Res Treat 2010;42:37\u201341. https:\/\/doi.org\/10.4143\/crt.2010.42.1.37.","DOI":"10.4143\/crt.2010.42.1.37"},{"key":"2025121815520082383_j_almed-2024-0069_ref_019","doi-asserted-by":"crossref","unstructured":"Soverini, S, Colarossi, S, Gnani, A, Rosti, G, Castagnetti, F, Poerio, 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. https:\/\/doi.org\/10.1158\/1078-0432.CCR-06-1516.","DOI":"10.1158\/1078-0432.CCR-06-1516"},{"key":"2025121815520082383_j_almed-2024-0069_ref_020","doi-asserted-by":"crossref","unstructured":"Elsir, KH, Ahmed, MB, Yousef, NB, Ali, WH. Prevalence of BCR-ABL T315I mutation in different chronic myeloid leukemia patients categories. Pak J Biol Sci 2022;25:175\u201381. https:\/\/doi.org\/10.3923\/pjbs.2022.175.181.","DOI":"10.3923\/pjbs.2022.175.181"},{"key":"2025121815520082383_j_almed-2024-0069_ref_021","doi-asserted-by":"crossref","unstructured":"Hasford, J, Baccarani, M, Hoffmann, V, Guilhot, J, Saussele, S, Rosti, G, et al.. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 2011;118:686\u201392. https:\/\/doi.org\/10.1182\/blood-2010-12-319038.","DOI":"10.1182\/blood-2010-12-319038"},{"key":"2025121815520082383_j_almed-2024-0069_ref_022","doi-asserted-by":"crossref","unstructured":"Milojkovic, D, Apperley, J. Mechanisms of resistance to imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia. Clin Cancer Res 2009;15:7519\u201327. https:\/\/doi.org\/10.1158\/1078-0432.CCR-09-1068.","DOI":"10.1158\/1078-0432.CCR-09-1068"},{"key":"2025121815520082383_j_almed-2024-0069_ref_023","doi-asserted-by":"crossref","unstructured":"Jabbour, E, Kantarjian, H, Jones, D, Breeden, M, Garcia-Manero, G, O\u2019Brien, S, et al.. Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood 2008;112:53\u20135. https:\/\/doi.org\/10.1182\/blood-2007-11-123950.","DOI":"10.1182\/blood-2007-11-123950"},{"key":"2025121815520082383_j_almed-2024-0069_ref_024","doi-asserted-by":"crossref","unstructured":"Chen, C, Xu, N, WanEr, W, Liang, L, Zhou, X, JiXian, H, et al.. The clinical characteristics and efficacy of chronic myeloid leukemia patients with T315I mutation. Blood 2018;132:5433. Supplement 1 https:\/\/doi.org\/10.1182\/blood-2018-99-114113.","DOI":"10.1182\/blood-2018-99-114113"},{"key":"2025121815520082383_j_almed-2024-0069_ref_025","doi-asserted-by":"crossref","unstructured":"Elnahass, YH. Abl kinase domain mutations in imatinib-treated Egyptian patients with chronic myeloid leukemia. J Leuk 2013;01:1\u20137. https:\/\/doi.org\/10.4172\/2329-6917.1000106.","DOI":"10.4172\/2329-6917.1000106"},{"key":"2025121815520082383_j_almed-2024-0069_ref_026","doi-asserted-by":"crossref","unstructured":"Mauro, MJ, Cortes, JE, Kim, D-W, Pinilla-Ibarz, J, le Coutre, P, Paquette, R, et al.. Multivariate analyses of the clinical and molecular parameters associated with efficacy and safety in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) treated with ponatinib in the PACE trial. 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