{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:55:33Z","timestamp":1771563333366,"version":"3.50.1"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T00:00:00Z","timestamp":1717286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DAAD scholarship program, bi-nationally supervised doctoral degrees","award":["2018\/19 (57381333)"],"award-info":[{"award-number":["2018\/19 (57381333)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Tyrosine kinase inhibitor (TKI) drugs have significantly improved chronic myeloid leukemia (CML) outcomes. Neopeptides from CML cells may induce specific immune responses, which are crucial for deep molecular (DMR) and treatment-free remission (TFR). In this study of Ethiopian patients with CML (n = 162), the HLA alleles and single-nucleotide polymorphisms of five cytokines revealed significant associations with clinical outcomes. Clinically unfavorable outcomes correlated with HLA alleles A*03:01\/02, A*23:17:01, B*57:01\/02\/03, and HLA-DRB4*01:01 (p-value = 0.0347, p-value = 0.0285, p-value = 0.037, and p-value = 0.0127, respectively), while HLA-DRB4*01:03:01 was associated with favorable outcomes (p-value = 0.0058). After assigning values for the \u2018low\u2019, \u2018intermediate\u2019, and \u2018high\u2019 gene expression of the SNPs\u2019 respective cytokine genes, Kaplan\u2013Meier estimates for relapse-free survival, adjusted for age, treatment duration, and relapse risk among patients after the administration of TKIs, indicated that a gene expression ratio above the overall median of TNF-\u03b1, IL-6, and the combination of TGF-\u03b21\/IL-10, IFN\u03b3, and IL-6\/IL-10 TGF-\u03b21 was correlated with a higher likelihood of treatment failure ((RR: 3.01; 95% CI: 1.1\u20138.3; p-value = 0.0261) and (RR: 2.4; 95% CI: 1.1\u20135.2; p-value = 0.022), respectively). Multi-SNPs, surpassing single-SNPs, and HLA allele polymorphisms showed promise in predicting outcomes of patients with CML during TKI treatment, prompting further exploration into their potential utility.<\/jats:p>","DOI":"10.3390\/genes15060732","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T10:08:38Z","timestamp":1717409318000},"page":"732","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prognostic Role of Human Leukocyte Antigen Alleles and Cytokine Single-Nucleotide Polymorphisms in Patients with Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitor Drugs"],"prefix":"10.3390","volume":"15","author":[{"given":"Samuel Kinde","family":"Birru","sequence":"first","affiliation":[{"name":"Jos\u00e9 Carreras Research Laboratory, Department of Hematology and Cell Therapy, Faculty of Medicine, University of Leipzig, Johannisallee 32A, 04103 Leipzig, Germany"},{"name":"Armauer Hansen Research Institute, Addis Ababa P.O. Box 1005, Ethiopia"},{"name":"College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilias","family":"Doxiadis","sequence":"additional","affiliation":[{"name":"Laboratory for Transplantation Immunology, University Hospital Leipzig, Johannisallee 32, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rawleigh","family":"Howe","sequence":"additional","affiliation":[{"name":"Armauer Hansen Research Institute, Addis Ababa P.O. Box 1005, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsehayneh","family":"Kelemu","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saifu Hailu","family":"Chala","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"},{"name":"Medical Laboratory Scienec, Madda Walabu University, Bale Robe P.O. Box 247, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0200-3024","authenticated-orcid":false,"given":"Abdulaziz","family":"Sherif","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fisihatsion","family":"Tadesse","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aster","family":"Tsegaye","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amha","family":"Gebremedhin","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2791-764X","authenticated-orcid":false,"given":"Claudia","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Laboratory for Transplantation Immunology, University Hospital Leipzig, Johannisallee 32, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1182\/blood.V96.10.3343","article-title":"The molecular biology of chronic myeloid leukemia","volume":"96","author":"Deininger","year":"2000","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood.V83.8.2038.2038","article-title":"Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia","volume":"83","author":"Bedi","year":"1994","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","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 J. 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