{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:59:37Z","timestamp":1784591977022,"version":"3.55.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Chronic myeloid leukemia is a malignancy of bone marrow that affects white blood cells. There is strong evidence that disease progression, treatment responses, and overall clinical outcomes of CML patients are influenced by the accumulation of other genetic and epigenetic abnormalities, rather than only the BCR\/ABL1 oncoprotein. Both genetic and epigenetic factors influence the efficacy of CML treatment strategies. Targeted medicines known as tyrosine-kinase inhibitors have dramatically improved long-term survival rates in CML patients during the previous 2\u00a0decades. When compared to earlier chemotherapy treatments, these drugs have revolutionized CML treatment and allowed most people to live longer lives. Although epigenetic inhibitors\u2019 activity is disrupted in many cancers, including CML, but when combined with TKI, they may offer potential therapeutic strategies for the treatment of CML cells. The epigenetics of tyrosine kinase inhibitors and resistance to them is being studied, with a particular focus on imatinib, which is used to treat CML. In addition, the use of epigenetic drugs in conjunction with TKIs has been discussed. Resistance to TKIs is still a problem in curing the disease, necessitating the development of new therapies. This study focused on epigenetic pathways involved in CML pathogenesis and tumor cell resistance to TKIs, both of which contribute to leukemic clone breakout and proliferation.<\/jats:p>","DOI":"10.3389\/fgene.2021.742802","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T07:08:31Z","timestamp":1634886511000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["A Review on the Therapeutic Role of TKIs in Case of CML in Combination With Epigenetic Drugs"],"prefix":"10.3389","volume":"12","author":[{"given":"Mohd","family":"Amir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleem","family":"Javed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1002\/ajh.25939","article-title":"Phase I\/II Study of Dasatinib in Combination with Decitabine in Patients with Accelerated or Blast Phase Chronic Myeloid Leukemia","volume":"95","author":"Abaza","year":"2020","journal-title":"Am. J. Hematol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1111\/bjh.16245","article-title":"Sudden Blastic Transformation in Treatment\u2010free Remission Chronic Myeloid Leukaemia","volume":"187","author":"Alfayez","year":"2019","journal-title":"Br. J. Haematol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3934","DOI":"10.1080\/07391102.2020.1772880","article-title":"Biomolecular Interactions and Binding Dynamics of Tyrosine Kinase Inhibitor Erdafitinib, with Human Serum Albumin","volume":"39","author":"Amir","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B77","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 Revision to the World Health Organization Classification of Myeloid Neoplasms and Acute Leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1182\/blood-2013-05-501569","article-title":"European LeukemiaNet Recommendations for the Management of Chronic Myeloid Leukemia: 2013","volume":"122","author":"Baccarani","year":"2013","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.ddtec.2014.03.003","article-title":"Current Aspects in Resistance against Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukemia","volume":"11","author":"Balabanov","year":"2014","journal-title":"Drug Discov. Today Tech."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1177\/1078155220953198","article-title":"Outcome of COVID-19 in Patients with Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitors","volume":"26","author":"Ba\u015fc\u0131","year":"2020","journal-title":"J. Oncol. Pharm. Pract."},{"key":"B78","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S1359-6446(04)03309-4","article-title":"Histone Deacetylase Inhibitors: New Drugs for the Treatment of Inflammatory Diseases?","volume":"10","author":"Blanchard","year":"2005","journal-title":"Drug Discov. Today"},{"key":"B8","unstructured":"Bosutinib. US FDA1172017"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1200\/JCO.2015.66.2866","article-title":"Life Expectancy of Patients with Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population","volume":"34","author":"Bower","year":"2016","journal-title":"Jco"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcell.2019.00136","article-title":"Epigenetic Reprogramming and Emerging Epigenetic Therapies in CML","volume":"7","author":"Bugler","year":"2019","journal-title":"Front. Cel Dev. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"308308","DOI":"10.1097\/MOH.0b013e328360ab64","article-title":"Roles of SIRT1 in Leukemogenesis","volume":"20","author":"Chen","year":"2013","journal-title":"Curr. Opin. Hematol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1158\/1078-0432.CCR-10-1613","article-title":"Molecular Pathways: BCR-ABL","volume":"18","author":"Cilloni","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"B79","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.exphem.2008.11.004","article-title":"Proteasome Proteolytic Profile is Linked to Bcr-Abl Expression","volume":"37","author":"Crawford","year":"2009","journal-title":"Exp. Hematol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1083\/jcb.201808028","article-title":"Polycomb Complexes in normal and Malignant Hematopoiesis","volume":"218","author":"Di Carlo","year":"2019","journal-title":"J. Cel Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/nature09883","article-title":"BCL6 Enables Ph+ Acute Lymphoblastic Leukaemia Cells to Survive BCR-ABL1 Kinase Inhibition","volume":"473","author":"Duy","year":"2011","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/129715","article-title":"HOXA4Gene Promoter Hypermethylation as an Epigenetic Mechanism Mediating Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia Patients","volume":"2013","author":"Elias","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"B18","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/nrg1748","article-title":"The Epigenetic Progenitor Origin of Human Cancer","volume":"7","author":"Feinberg","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/301089a0","article-title":"Hypomethylation Distinguishes Genes of Some Human Cancers from Their normal Counterparts","volume":"301","author":"Feinberg","year":"1983","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.1002\/tcr.201800091","article-title":"Six Years (2012-2018) of Researches on Catalytic EZH2 Inhibitors: The Boom of the 2\u2010Pyridone Compounds","volume":"18","author":"Fioravanti","year":"2018","journal-title":"Chem. Rec."},{"key":"B21","unstructured":"Gleevec (Imatinib Mesylate) FDA US2008"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1080\/10428194.2018.1430795","article-title":"Enhancer of Zeste Homolog 2 (EZH2) Inhibitors","volume":"59","author":"Gulati","year":"2018","journal-title":"Leuk. Lymphoma."},{"key":"B26","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.celrep.2013.06.016","article-title":"A Hybrid Mechanism of Action for BCL6 in B Cells Defined by Formation of Functionally Distinct Complexes at Enhancers and Promoters","volume":"4","author":"Hatzi","year":"2013","journal-title":"Cel Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"110390","DOI":"10.1016\/j.biopha.2020.110390","article-title":"A Novel HDAC Inhibitor Chidamide Combined with Imatinib Synergistically Targets Tyrosine Kinase Inhibitor Resistant Chronic Myeloid Leukemia Cells","volume":"129","author":"He","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 Recommendations for Treating Chronic Myeloid Leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.3390\/cancers6031769","article-title":"Drug Resistance in Cancer: An Overview","volume":"6","author":"Housman","year":"2014","journal-title":"CancersMDPI AG"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1182\/blood-2013-06-510396","article-title":"Early Molecular Response Predicts Outcomes in Patients with Chronic Myeloid Leukemia in Chronic Phase Treated with Frontline Nilotinib or Imatinib","volume":"123","author":"Hughes","year":"2014","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1084\/jem.20110304","article-title":"BCL6-mediated Repression of P53 Is Critical for Leukemia Stem Cell Survival in Chronic Myeloid Leukemia","volume":"208","author":"Hurtz","year":"2011","journal-title":"J. Exp. Med."},{"key":"B33","unstructured":"Ponatinib. FDA US32016"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1182\/blood-2017-07-792143","article-title":"Clonal Chromosomal Abnormalities Appearing in Philadelphia Chromosome-Negative Metaphases during CML Treatment","volume":"130","author":"Issa","year":"2017","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1002\/ajh.25792","article-title":"Chronic Myeloid Leukemia: 2020 Update on Diagnosis, Therapy and Monitoring","volume":"95","author":"Jabbour","year":"2020","journal-title":"Am. J. Hematol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.leukres.2010.04.001","article-title":"Combined Proteasome and Histone Deacetylase Inhibition: A Promising Synergy for Patients with Relapsed\/refractory Multiple Myeloma","volume":"34","author":"Jagannath","year":"2010","journal-title":"Leuk. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/S2352-3026(15)00021-6","article-title":"Analysis of Long Term Responses and Their Impact on Outcomes in Patients with Chronic Phase CML Treated with Four Different TKI Modalities \u2013 Analysis of 5 Prospective Clinical Trials","volume":"2","author":"Jain","year":"2015","journal-title":"Lancet Haematol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1182\/bloodadvances.2018025874","article-title":"Analysis of Cardiovascular and Arteriothrombotic Adverse Events in Chronic-phase CML Patients after Frontline TKIs","volume":"3","author":"Jain","year":"2019","journal-title":"Blood Adv."},{"key":"B39","doi-asserted-by":"publisher","first-page":"4391","DOI":"10.1002\/cncr.30864","article-title":"Prognostic Factors and Survival Outcomes in Patients with Chronic Myeloid Leukemia in Blast Phase in the Tyrosine Kinase Inhibitor Era: Cohort Study of 477 Patients","volume":"123","author":"Jain","year":"2017","journal-title":"Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/bjh.13936","article-title":"Analysis of 2013 European LeukaemiaNet (ELN) Responses in Chronic Phase CML across Four Frontline TKI Modalities and Impact on Clinical Outcomes","volume":"173","author":"Jain","year":"2016","journal-title":"Br. J. Haematol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/nejmoa1701719","article-title":"Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease","volume":"377","author":"Jaiswal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"22110","DOI":"10.1371\/journal.pone.0022110","article-title":"Aberrant DNA Methylation is Associated with Disease Progression, Resistance to Imatinib and Shortened Survival in Chronic Myelogenous Leukemia","volume":"6","author":"Jelinek","year":"2011","journal-title":"PLoS One"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1056\/NEJMoa1002315","article-title":"Dasatinib versus Imatinib in Newly Diagnosed Chronic-phase Chronic Myeloid Leukemia","volume":"362","author":"Kantarjian","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13148-020-00839-z","article-title":"Novel HDAC Inhibitor MAKV-8 and Imatinib Synergistically Kill Chronic Myeloid Leukemia Cells via Inhibition of BCR-ABL\/MYC-signaling: Effect on Imatinib Resistance and Stem Cells","volume":"12","author":"Lernoux","year":"2020","journal-title":"Clin. Epigenet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.ccr.2011.12.020","article-title":"Activation of P53 by SIRT1 Inhibition Enhances Elimination of CML Leukemia Stem Cells in Combination with Imatinib","volume":"21","author":"Li","year":"2012","journal-title":"Cancer Cell."},{"key":"B45","doi-asserted-by":"publisher","first-page":"5349","DOI":"10.2147\/CMAR.S166859","article-title":"Epigenetic Regulation of HOTAIR in Advanced Chronic Myeloid Leukemia","volume":"10","author":"Li","year":"2018","journal-title":"Cmar"},{"key":"B46","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1046\/j.1365-2141.2003.04660.x","article-title":"Epigenetic Alteration of theSOCS1gene in Chronic Myeloid Leukaemia","volume":"123","author":"Liu","year":"2003","journal-title":"Br. J. Haematol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4619","DOI":"10.1038\/onc.2017.85","article-title":"Interferon \u03b3 Is a STAT1-dependent Direct Inducer of BCL6 Expression in Imatinib-Treated Chronic Myeloid Leukemia Cells","volume":"36","author":"Madapura","year":"2017","journal-title":"Oncogene"},{"key":"B48","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1159\/000506346","article-title":"Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias","volume":"143","author":"Maiti","year":"2020","journal-title":"Acta Haematol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1111\/cas.12965","article-title":"Combination of Panobinostat with Ponatinib Synergistically Overcomes Imatinib\u2010resistant CML Cells","volume":"107","author":"Matsuda","year":"2016","journal-title":"Cancer Sci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"5097","DOI":"10.1021\/jm0303094","article-title":"Histone Deacetylase Inhibitors","volume":"46","author":"Miller","year":"2003","journal-title":"J. Med. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1200\/JCO.2010.32.7114","article-title":"Imatinib Is Effective in Children with Previously Untreated Chronic Myelogenous Leukemia in Early Chronic Phase: Results of the French National Phase IV Trial","volume":"29","author":"Millot","year":"2011","journal-title":"Jco"},{"key":"B52","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.clml.2020.12.025","article-title":"Clinical Outcomes of Patients with Chronic Myeloid Leukemia with Concurrent Core Binding Factor Rearrangement and Philadelphia Chromosome","volume":"21","author":"Morita","year":"","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1002\/cncr.33539","article-title":"Outcome of Patients with Chronic Myeloid Leukemia in Lymphoid Blastic Phase and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated with hyper\u2010CVAD and Dasatinib","volume":"127","author":"Morita","year":"","journal-title":"Cancer"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.2174\/156802610792232079","article-title":"Macrocyclic Histone Deacetylase Inhibitors","volume":"10","author":"Mwakwari","year":"2010","journal-title":"Curr. Top. Med. Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2400","DOI":"10.3324\/haematol.2018.200220","article-title":"Somatic Variants in Epigenetic Modifiers Can Predict Failure of Response to Imatinib but Not to Second-Generation Tyrosine Kinase Inhibitors","volume":"104","author":"Nteliopoulos","year":"2019","journal-title":"Haematologica"},{"key":"B56","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.ccr.2009.09.028","article-title":"AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance","volume":"16","author":"O'Hare","year":"2009","journal-title":"Cancer Cell."},{"key":"B57","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1002\/cncr.22470","article-title":"Phase II Study of Low-Dose Decitabine in Combination with Imatinib Mesylate in Patients with Accelerated or Myeloid Blastic Phase of Chronic Myelogenous Leukemia","volume":"109","author":"Oki","year":"2007","journal-title":"Cancer"},{"key":"B58","doi-asserted-by":"publisher","first-page":"106337","DOI":"10.1016\/J.LEUKRES.2020.106337","article-title":"Novel Therapeutic Approaches in Chronic Myeloid Leukemia","volume":"91","author":"\u00d6zg\u00fcr Yurtta\u015f","year":"2020","journal-title":"Leuk. Res."},{"key":"B82","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.bmc.2009.10.042","article-title":"Antimalarial and Antileishmanial Activities of Histone Deacetylase Inhibitors with Triazole-Linked Cap Group","volume":"18","author":"Patil","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"B59","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1177\/1947601912462126","article-title":"The Ins and Outs of Bcr-Abl Inhibition","volume":"3","author":"Reddy","year":"2012","journal-title":"Genes. Cancer"},{"key":"B60","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.beha.2009.07.007","article-title":"Epidemiology of Chronic Myeloid Leukaemia (CML)","volume":"22","author":"Rohrbacher","year":"2009","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.3390\/jcm9061709","article-title":"Chronic Myeloid Leukemia Prognosis and Therapy: Criticisms and Perspectives","volume":"9","author":"Russo","year":"2020","journal-title":"Jcm"},{"key":"B62","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1056\/nejmoa0912614","article-title":"Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia","volume":"362","author":"Saglio","year":"2010","journal-title":"New Engl. J. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1016\/j.ejca.2009.04.005","article-title":"Epigenetic Down-Regulation of BIM Expression Is Associated with Reduced Optimal Responses to Imatinib Treatment in Chronic Myeloid Leukaemia","volume":"45","author":"San Jos\u00e9-Eneriz","year":"2009","journal-title":"Eur. J. Cancer."},{"key":"B64","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1002\/cncr.29745","article-title":"Conditional Survival in Patients with Chronic Myeloid Leukemia in Chronic Phase in the Era of Tyrosine Kinase Inhibitors","volume":"122","author":"Sasaki","year":"2016","journal-title":"Cancer"},{"key":"B65","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/s12185-019-02620-2","article-title":"Incidence of Second Malignancies in Patients with Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors","volume":"109","author":"Sasaki","year":"2019","journal-title":"Int. J. Hematol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1002\/cncr.31187","article-title":"Prediction for Sustained Deep Molecular Response of BCR-ABL1 Levels in Patients with Chronic Myeloid Leukemia in Chronic Phase","volume":"124","author":"Sasaki","year":"2018","journal-title":"Cancer"},{"key":"B67","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/S2352-3026(15)00048-4","article-title":"Prospective Analysis: Relative Survival in Patients with Chronic Myeloid Leukemia in Chronic Phase in the Era of Tyrosine Kinase Inhibitors","volume":"2","author":"Sasaki","year":"2015","journal-title":"Lancet Haematol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13045-021-01106-1","article-title":"Impact of Frontline Treatment Approach on Outcomes of Myeloid Blast Phase CML","volume":"14","author":"Saxena","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1158\/2159-8290.CD-16-0263","article-title":"Epigenetic Reprogramming Sensitizes CML Stem Cells to Combined EZH2 and Tyrosine Kinase Inhibition","volume":"6","author":"Scott","year":"2016","journal-title":"Cancer Discov."},{"key":"B70","doi-asserted-by":"publisher","first-page":"7374","DOI":"10.1158\/1078-0432.CCR-06-1516","article-title":"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","volume":"12","author":"Soverini","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3324\/haematol.11248","article-title":"Targeted Therapy and the T315I Mutation in Philadelphia-positive Leukemias","volume":"92","author":"Soverini","year":"2007","journal-title":"Haematologica"},{"key":"B72","unstructured":"Dasatinib. FDA US1372010"},{"key":"B73","unstructured":"Nilotinib. US FDA2017"},{"key":"B83","doi-asserted-by":"publisher","first-page":"5495","DOI":"10.1158\/0008-5472.CAN-05-2385","article-title":"DNA Methylation Changes After 5-aza-2\u2032-deoxycytidine Therapy in Patients with Leukemia","volume":"66","author":"Yang","year":"2006","journal-title":"Cancer Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1182\/blood-2011-06-361691","article-title":"Activation of Stress Response Gene SIRT1 by BCR-ABL Promotes Leukemogenesis","volume":"119","author":"Yuan","year":"2012","journal-title":"Blood"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/CBIN.11557","article-title":"Abrogation of Histone Deacetylases (HDACs) Decreases Survival of Chronic Myeloid Leukemia Cells: New Insight into Attenuating Effects of the PI3K\/c-Myc axis on Panobinostat Cytotoxicity","volume":"45","author":"Zehtabcheh","year":"2021","journal-title":"Cel Biol. Int."},{"key":"B76","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1007\/s11596-020-2266-1","article-title":"AICAR and Decitabine Enhance the Sensitivity of K562 Cells to Imatinib by Promoting Mitochondrial Activity","volume":"40","author":"Zhu","year":"2020","journal-title":"Curr. Med. Sci."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.742802\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T07:08:48Z","timestamp":1634886528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.742802\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":75,"alternative-id":["10.3389\/fgene.2021.742802"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.742802","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]},"article-number":"742802"}}