{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:38:17Z","timestamp":1760146697471,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The long-term prognosis of acute myeloid leukemia (AML) is challenging due to limited understanding of the molecular markers involved in its development. This study investigates the role of DNA polymerases in AML to offer new insights for diagnosis and treatment. Materials and Methods: A retrospective study on pediatric AML patients with POL gene family mutations from 2021 to 2024 was conducted. Patients were categorized based on risk stratification criteria, and the DAH regimen was used for induction chemotherapy. Bioinformatics analysis integrated data from various databases to identify key genes and develop survival analysis plots and AUC curves. Results: The study included 59 pediatric AML patients, revealing no significant differences in demographic or clinical characteristics between those with and without POL family gene mutations. However, patients with POL gene mutations showed higher complete remission rates after initial DAH chemotherapy (91.67% vs. 59.57%, p = 0.03607), indicating a potential treatment benefit. High expression of four POL genes (POLD1, POLE, POLG, and POLQ) in bone marrow and immune cells suggests their crucial role in hematopoiesis and immune response. Survival analysis across different datasets indicated that AML patients with overexpressed POL family genes had significantly worse outcomes, proposing these genes as potential prognostic biomarkers for AML. Conclusions: This study on pediatric AML demonstrates that POL gene family mutations are associated with higher remission rates post-chemotherapy, indicating their potential as prognostic markers. Bioinformatics analysis emphasizes the significance of these mutations in AML, highlighting their impact on disease prognosis.<\/jats:p>","DOI":"10.3390\/medicina60121975","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T06:58:58Z","timestamp":1733122738000},"page":"1975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Analysis of Polymerase Family Gene Mutations in Acute Myeloid Leukemia: Clinical Features, Prognosis, and Bioinformatics Insights"],"prefix":"10.3390","volume":"60","author":[{"given":"Jianrong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoban","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, West China Second University Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.blre.2016.08.005","article-title":"Molecular biomarkers in acute myeloid leukemia","volume":"31","author":"Arroyave","year":"2017","journal-title":"Blood Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1182\/blood-2012-03-362608","article-title":"Diagnosis and management of acute myeloid leukemia in children and adolescents: Recommendations from an international expert panel","volume":"120","author":"Creutzig","year":"2012","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ksiazek, T., Czogala, M., Kaczowka, P., Sadowska, B., Pawinska-Wasikowska, K., Bik-Multanowski, M., Sikorska-Fic, B., Matysiak, M., Skalska-Sadowska, J., and Wachowiak, J. (2020). High Frequency of Fusion Gene Transcript Resulting From t(10;11)(p12;q23) Translocation in Pediatric Acute Myeloid Leukemia in Poland. Front. Pediatr., 8.","DOI":"10.3389\/fped.2020.00278"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nrg2345","article-title":"DNA polymerases and human disease","volume":"9","author":"Loeb","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/path.5081","article-title":"Somatic POLE exonuclease domain mutations are early events in sporadic endometrial and colorectal carcinogenesis, determining driver mutational landscape, clonal neoantigen burden and immune response","volume":"245","author":"Temko","year":"2018","journal-title":"J. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1097\/DCR.0000000000001150","article-title":"POLD1 and POLE Gene Mutations in Jewish Cohorts of Early-Onset Colorectal Cancer and of Multiple Colorectal Adenomas","volume":"61","author":"Rosner","year":"2018","journal-title":"Dis. Colon. Rectum"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s10689-018-0102-6","article-title":"Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma","volume":"18","author":"Siegfried","year":"2019","journal-title":"Fam. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4587","DOI":"10.1002\/cam4.2344","article-title":"Clinicopathological and mutational analyses of colorectal cancer with mutations in the POLE gene","volume":"8","author":"Hino","year":"2019","journal-title":"Cancer Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ygyno.2019.10.028","article-title":"Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer","volume":"156","author":"Stasenko","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ygyno.2014.05.006","article-title":"POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium","volume":"134","author":"Meng","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma","volume":"497","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/jnci\/dju402","article-title":"Prognostic significance of POLE proofreading mutations in endometrial cancer","volume":"107","author":"Church","year":"2015","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/modpathol.2014.143","article-title":"Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations","volume":"28","author":"Hussein","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1038\/s41467-023-38160-x","article-title":"DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing M.Y.C","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/s41423-020-0425-8","article-title":"Pedigree analysis of a POLD1 germline mutation in urothelial carcinoma shows a close association between different mutation burdens and overall survival","volume":"18","author":"Wang","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13390","DOI":"10.1073\/pnas.0910759107","article-title":"DNA polymerase theta up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability","volume":"107","author":"Bergoglio","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"175","DOI":"10.18632\/oncotarget.124","article-title":"Overexpression of POLQ confers a poor prognosis in early breast cancer patients","volume":"1","author":"Higgins","year":"2010","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shinmura, K., Kato, H., Kawanishi, Y., Yoshimura, K., Tsuchiya, K., Takahara, Y., Hosokawa, S., Kawase, A., Funai, K., and Sugimura, H. (2019). POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma. Cancers, 11.","DOI":"10.3390\/cancers11050722"},{"key":"ref_19","first-page":"523","article-title":"Enhanced expression and activity of DNA polymerase beta in chronic myelogenous leukemia","volume":"26","author":"Canitrot","year":"2006","journal-title":"Anticancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/S1470-2045(21)00328-4","article-title":"Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): An open-label, multicentre, randomised, phase 3, non-inferiority trial","volume":"22","author":"Yang","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11912-020-01009-3","article-title":"Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy","volume":"23","author":"Conneely","year":"2021","journal-title":"Curr. Oncol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/ajh.26822","article-title":"Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management","volume":"98","author":"Shimony","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/s12185-011-0837-4","article-title":"Homoharringtonine as a backbone drug for the treatment of newly diagnosed pediatric acute myeloid leukemia: A report from a single institution in China","volume":"93","author":"Tang","year":"2011","journal-title":"Int. J. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1200\/JCO.22.02836","article-title":"Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood A.M.L. A Report From the CCLG-AML 2015 Protocol Study","volume":"41","author":"Li","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_25","first-page":"373","article-title":"Clinical Analysis of Pediatric Acute Myeloid Leukemia with CCLG-AML 2015 Regimen","volume":"30","author":"Wang","year":"2022","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Liu, L., Nie, Q., Xiao, Z., Chen, X., Yang, C., Mao, X., Li, N., Zhou, Y., Guo, Q., and Tian, X. (2024). Treatment of three pediatric AML co-expressing NUP98-NSD1, FLT3-ITD, and WT1. BMC Pediatr., 24.","DOI":"10.1186\/s12887-024-04954-1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.1007\/s00277-024-05939-x","article-title":"Investigation of infections status in pediatric patients with acute myeloid leukemia during the induction period-a retrospective study in two medical centers","volume":"103","author":"Xu","year":"2024","journal-title":"Ann. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e28037","DOI":"10.1016\/j.heliyon.2024.e28037","article-title":"Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis","volume":"10","author":"Wu","year":"2024","journal-title":"Heliyon"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e24830","DOI":"10.1002\/jcla.24830","article-title":"Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature","volume":"37","author":"Wu","year":"2023","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.21037\/tcr-21-2853","article-title":"Prognostic and immunological significance of peroxisome proliferator-activated receptor gamma in hepatocellular carcinoma based on multiple databases","volume":"11","author":"Wang","year":"2022","journal-title":"Transl. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1038\/s41375-018-0071-7","article-title":"Successes and challenges in the treatment of pediatric acute myeloid leukemia: A retrospective analysis of the AML-BFM trials from 1987 to 2012","volume":"32","author":"Rasche","year":"2018","journal-title":"Leukemia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3324\/haematol.2022.280801","article-title":"The clinical impact of the molecular landscape of acute myeloid leukemia","volume":"108","author":"Kayser","year":"2023","journal-title":"Haematologica"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yue, C., Xie, S., Zhong, J., Zhao, H., Lin, Z., Zhang, L., Xu, B., and Luo, Y. (2021). SCAMP2\/5 as diagnostic and prognostic markers for acute myeloid leukemia. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-96440-2"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/1975\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:44:07Z","timestamp":1760114647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/1975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,1]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["medicina60121975"],"URL":"https:\/\/doi.org\/10.3390\/medicina60121975","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2024,12,1]]}}}