{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:53:45Z","timestamp":1791312825019,"version":"4.3.1"},"reference-count":64,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["1R15GM137288"],"award-info":[{"award-number":["1R15GM137288"]}]},{"name":"National Institutes of Health","award":["Award No. OIA-1946391"],"award-info":[{"award-number":["Award No. OIA-1946391"]}]},{"name":"National Institutes of Health","award":["P20GM10342"],"award-info":[{"award-number":["P20GM10342"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1R15GM137288"],"award-info":[{"award-number":["1R15GM137288"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["Award No. OIA-1946391"],"award-info":[{"award-number":["Award No. OIA-1946391"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["P20GM10342"],"award-info":[{"award-number":["P20GM10342"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R15GM137288"],"award-info":[{"award-number":["1R15GM137288"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Award No. OIA-1946391"],"award-info":[{"award-number":["Award No. OIA-1946391"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM10342"],"award-info":[{"award-number":["P20GM10342"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by a unique BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) were developed to target the BCR-ABL oncoprotein, inhibiting its abnormal kinase activity. TKI treatments have significantly improved CML patient outcomes. However, the patients can develop drug resistance and relapse after therapy discontinues largely due to intratumor heterogeneity. It is critical to understand the differences in therapeutic responses among subpopulations of cells. Single-cell RNA sequencing measures the transcriptome of individual cells, allowing us to differentiate and analyze individual cell populations. Here, we integrated a single-cell RNA sequencing profile of CML stem cells and network analysis to decipher the mechanisms of distinct TKI responses. Compared to normal hematopoietic stem cells, a set of genes that were concordantly differentially expressed in various types of stem cells of CML patients was revealed. Further transcription regulatory network analysis found that most of these genes were directly controlled by one or more transcript factors and the genes have more regulators in the cells of the patients who responded to the treatment. The molecular markers including a known drug-resistance gene and novel gene signatures for treatment response were also identified. Moreover, we combined protein\u2013protein interaction network construction with a cancer drug database and uncovered the drugs that target the marker genes directly or indirectly via the protein interactions. The gene signatures and their interacted proteins identified by this work can be used for treatment response prediction and lead to new strategies for drug resistance monitoring and prevention. Our single-cell-based findings offered novel insights into the mechanisms underlying the therapeutic response of CML.<\/jats:p>","DOI":"10.3390\/ijms232214335","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T02:52:21Z","timestamp":1668999141000},"page":"14335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Integrating Single-Cell Transcriptome and Network Analysis to Characterize the Therapeutic Response of Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"23","author":[{"given":"Jialu","family":"Ma","sequence":"first","affiliation":[{"name":"MidSouth Bioinformatics Center and Joint Bioinformatics Graduate Program, University of Arkansas at Little Rock, University of Arkansas for Medical Sciences, Little Rock, AR 72204, USA"},{"name":"Department of Information Science, University of Arkansas at Little Rock, Little Rock, AR 72204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Pettit","sequence":"additional","affiliation":[{"name":"Department of Philosophy and Interdisciplinary Studies, University of Arkansas at Little Rock, Little Rock, AR 72204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-0965","authenticated-orcid":false,"given":"John","family":"Talburt","sequence":"additional","affiliation":[{"name":"Department of Information Science, University of Arkansas at Little Rock, Little Rock, AR 72204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7068-0756","authenticated-orcid":false,"given":"Shanzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. John\u2019s University, Queens, NY 11439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherman M.","family":"Weissman","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Qu","family":"Yang","sequence":"additional","affiliation":[{"name":"MidSouth Bioinformatics Center and Joint Bioinformatics Graduate Program, University of Arkansas at Little Rock, University of Arkansas for Medical Sciences, Little Rock, AR 72204, USA"},{"name":"Department of Information Science, University of Arkansas at Little Rock, Little Rock, AR 72204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/ejh.12743","article-title":"Population-based assessment of chronic myeloid leukemia in Sweden: Striking increase in survival and prevalence","volume":"97","author":"Gunnarsson","year":"2016","journal-title":"Eur. J. Haematol."},{"key":"ref_2","first-page":"433","article-title":"Comprehensive analysis of BCR\/ABL variants in chronic myeloid leukemia patients using multiplex RT-PCR","volume":"58","author":"Bennour","year":"2012","journal-title":"Clin. Lab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8547","DOI":"10.1038\/sj.onc.1206082","article-title":"BCR\/ABL: From molecular mechanisms of leukemia induction to treatment of chronic myelogenous leukemia","volume":"21","author":"Salesse","year":"2002","journal-title":"Oncogene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11899-019-00524-w","article-title":"Is there a role for dose modification of TKI therapy in CML?","volume":"14","author":"Copland","year":"2019","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.3109\/10428194.2013.845883","article-title":"Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia","volume":"55","author":"Jabbour","year":"2014","journal-title":"Leuk. Lymphoma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100257","DOI":"10.1016\/j.eclinm.2020.100257","article-title":"The survival of patients enrolled in a global direct-to-patient cancer medicine donation program: The Glivec International Patient Assistance Program (GIPAP)","volume":"19","author":"Umeh","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1056\/NEJMoa1609324","article-title":"Long-term outcomes of imatinib treatment for chronic myeloid leukemia","volume":"376","author":"Hochhaus","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.ccell.2020.03.006","article-title":"Response and resistance to BCR-ABL1-targeted therapies","volume":"37","author":"Braun","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/MOH.0000000000000403","article-title":"Resistance in chronic myeloid leukemia: Definitions and novel therapeutic agents","volume":"25","author":"Talati","year":"2018","journal-title":"Curr. Opin. Hematol."},{"key":"ref_10","first-page":"948","article-title":"Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease","volume":"132","author":"Branford","year":"2018","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1038\/bjc.2015.146","article-title":"Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: \u2018What does not kill me strengthens me\u2019","volume":"112","author":"Pisco","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ebiom.2016.01.007","article-title":"Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma","volume":"4","author":"Biddle","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12929-018-0426-4","article-title":"Cancer stem cells as key drivers of tumour progression","volume":"25","author":"Ayob","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1056\/NEJMoa0912228","article-title":"Persistent malignant stem cells in del (5q) myelodysplasia in remission","volume":"363","author":"Tehranchi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.ccr.2014.03.036","article-title":"Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo","volume":"25","author":"Woll","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ccr.2012.03.003","article-title":"Cancer stem cells: Impact, heterogeneity, and uncertainty","volume":"21","author":"Magee","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_17","first-page":"1595","article-title":"The chronic myeloid leukemia stem cell: Stemming the tide of persistence","volume":"129","author":"Holyoake","year":"2017","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_18","first-page":"5565","article-title":"Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment","volume":"118","author":"Chu","year":"2011","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_19","first-page":"951","article-title":"Hurdles toward a cure for CML: The CML stem cell","volume":"25","author":"Gallipoli","year":"2011","journal-title":"Hematol. Clin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1470-2045(10)70233-3","article-title":"Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial","volume":"11","author":"Mahon","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ccell.2015.04.004","article-title":"Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells","volume":"27","author":"Welner","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.ccr.2011.10.012","article-title":"IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development","volume":"20","author":"Reynaud","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nm.4336","article-title":"Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia","volume":"23","author":"Giustacchini","year":"2017","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3389\/fonc.2019.00939","article-title":"BCR-ABL independent mechanisms of resistance in chronic myeloid leukemia","volume":"9","author":"Loscocco","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_25","first-page":"489","article-title":"Effects of Cdc42 overexpression on the estrogen-enhanced multidrug resistance in breast cancer cells","volume":"33","author":"Jiang","year":"2011","journal-title":"Zhonghua Zhong Liu Za Zhi [Chin. J. Oncol.]"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41417-019-0109-7","article-title":"PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: A multiomics analysis","volume":"27","author":"Saha","year":"2020","journal-title":"Cancer Gene Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liu, F., Gore, A.J., Wilson, J.L., and Korc, M. (2014). DUSP1 is a novel target for enhancing pancreatic cancer cell sensitivity to gemcitabine. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084982"},{"key":"ref_28","first-page":"1203","article-title":"DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer","volume":"40","author":"Teng","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1002\/cam4.772","article-title":"Role of DUSP1\/MKP1 in tumorigenesis, tumor progression and therapy","volume":"5","author":"Shen","year":"2016","journal-title":"Cancer Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"198","DOI":"10.18632\/genesandcancer.182","article-title":"Common ELF1 deletion in prostate cancer bolsters oncogenic ETS function, inhibits senescence and promotes docetaxel resistance","volume":"9","author":"Budka","year":"2018","journal-title":"Genes Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1477-5956-9-76","article-title":"S100A10 protein expression is associated with oxaliplatin sensitivity in human colorectal cancer cells","volume":"9","author":"Suzuki","year":"2011","journal-title":"Proteome Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22876","DOI":"10.18632\/oncotarget.15283","article-title":"Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma","volume":"8","author":"Florea","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12014-015-9080-y","article-title":"Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer","volume":"12","author":"Johansson","year":"2015","journal-title":"Clin. Proteom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ygyno.2015.07.107","article-title":"Expression and clinical role of chemoresponse-associated genes in ovarian serous carcinoma","volume":"139","author":"Nymoen","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3389\/fphar.2021.627574","article-title":"An Open Access Database of Licensed Cancer Drugs","volume":"12","author":"Pantziarka","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"The AACR Project GENIE Consortium, Andr\u00e9, F., Arnedos, M., Baras, A.S., Baselga, J., Bedard, P.L., Berger, M.F., Bierkens, M., Calvo, F., and Cerami, E. (2017). AACR Project GENIE: Powering precision medicine through an international consortium. Cancer Discov., 7, 818\u2013831.","DOI":"10.1158\/2159-8290.CD-17-0151"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, Y.S., Gupta Vallur, P., Pha\u00ebton, R., Mythreye, K., and Hempel, N. (2017). Insights into the Dichotomous Regulation of SOD2 in Cancer. Antioxidants, 6.","DOI":"10.3390\/antiox6040086"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"353687","DOI":"10.1155\/2012\/353687","article-title":"The biochemistry and regulation of S100A10: A multifunctional plasminogen receptor involved in oncogenesis","volume":"2012","author":"Madureira","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","article-title":"The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights","volume":"335","author":"Coutinho","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1177\/1947601911408889","article-title":"Mutations in the p53 tumor suppressor gene: Important milestones at the various steps of tumorigenesis","volume":"2","author":"Rivlin","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40364-018-0136-9","article-title":"Kinomic profiling of glioblastoma cells reveals PLCG1 as a target in restricted glucose","volume":"6","author":"Walker","year":"2018","journal-title":"Biomark. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1158\/2159-8290.CD-19-0209","article-title":"Resistance mechanisms to SYK inhibition in acute myeloid leukemia","volume":"10","author":"Cremer","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00280-008-0791-x","article-title":"Targeting superoxide dismutase 1 to overcome cisplatin resistance in human ovarian cancer","volume":"63","author":"Brown","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_44","unstructured":"(2020, October 10). Gene Expression Omnibus, Available online: https:\/\/www.ncbi.nlm.nih.gov\/geo\/."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ramsk\u00f6ld, D., Wang, E.T., Burge, C.B., and Sandberg, R. (2009). An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000598"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D394","DOI":"10.1093\/nar\/gkaa1106","article-title":"PANTHER version 16: A revised family classification, tree-based classification tool, enhancer regions and extensive API","volume":"49","author":"Mi","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1038\/s41596-020-0336-2","article-title":"A scalable SCENIC workflow for single-cell gene regulatory network analysis","volume":"15","author":"Flerin","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1093\/bioinformatics\/bty916","article-title":"GRNBoost2 and Arboreto: Efficient and scalable inference of gene regulatory networks","volume":"35","author":"Moerman","year":"2019","journal-title":"Bioinformatics."},{"key":"ref_49","unstructured":"(2022, January 15). STRING: Functional Protein Association Networks. Available online: https:\/\/string-db.org\/."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3747\/co.v18i2.391","article-title":"Monitoring response and resistance to treatment in chronic myeloid leukemia","volume":"18","author":"Assouline","year":"2011","journal-title":"Curr. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/S1470-2045(07)70342-X","article-title":"Part I: Mechanisms of resistance to imatinib in chronic myeloid leukaemia","volume":"8","author":"Apperley","year":"2007","journal-title":"Lancet Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.coph.2006.10.001","article-title":"p11 (S100A10)\u2014An inducible adaptor protein that modulates neuronal functions","volume":"7","author":"Svenningsson","year":"2007","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/s41423-019-0278-1","article-title":"Essential roles of S100A10 in Toll-like receptor signaling and immunity to infection","volume":"17","author":"Lou","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.32607\/20758251-2010-2-3-21-29","article-title":"Toll-like receptors (TLRs): The role in tumor progression","volume":"3","author":"Shchebliakov","year":"2010","journal-title":"Acta Naturae."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ajhg.2015.11.014","article-title":"Genomic signatures of selective pressures and introgression from archaic hominins at human innate immunity genes","volume":"98","author":"Deschamps","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1111\/j.1398-9995.2007.01446.x","article-title":"Additive association between FCER1A and FCER1B genetic polymorphisms and total serum IgE levels","volume":"62","author":"Potaczek","year":"2007","journal-title":"Allergy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.rmed.2008.03.017","article-title":"Association of three sets of high-affinity IgE receptor (FcepsilonR1) polymorphisms with aspirin-intolerant asthma","volume":"102","author":"Palikhe","year":"2008","journal-title":"Respir. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1080\/15257770.2021.1964525","article-title":"Genetic association study of CTLA4 and FC\u03b5RI\u03b1 polymorphisms in asthmatic patients in the southwestern region of Iran","volume":"40","author":"Roshanizadeh","year":"2021","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1093\/carcin\/bgp084","article-title":"Candidate gene approach evaluates association between innate immunity genes and breast cancer risk in Korean women","volume":"30","author":"Lee","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"57932","DOI":"10.18632\/oncotarget.10773","article-title":"Anti-cancer effects of nitrogen-containing bisphosphonates on human cancer cells","volume":"7","author":"Jiang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/1476-4598-9-312","article-title":"Integrin-mediated function of Rab GTPases in cancer progression","volume":"9","author":"Subramani","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_63","unstructured":"American Cancer Society (2022, October 26). Cancer Facts & Figures 2022. Available online: https:\/\/www.cancer.org\/cancer\/chronic-myeloid-leukemia\/about\/statistics.html."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.3324\/haematol.2011.056721","article-title":"Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy","volume":"97","author":"Pemmaraju","year":"2012","journal-title":"Haematologica"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:21:27Z","timestamp":1760145687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":64,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214335"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214335","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]}}}