{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:20:30Z","timestamp":1788528030741,"version":"build-2803163510"},"reference-count":55,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cancer Control"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>IDH1 mutations are common in many cancers, however, their role in promoting the Warburg effect remains elusive. This study elucidates the putative involvement of mutant-IDH1 in regulating hypoxia-inducible factor (HIF1-\u03b1) and Sine-Oculis Homeobox-1 (SIX-1) expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Genetic screening was performed using the ARMS-PCR in acute myeloid leukemia (AML), brain, and breast cancer (BC) cohorts, while transcript expression was determined using qPCR. Further, a meta-analysis of risk factors associated with the R132 mutation was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Approximately 32% of AML and \u223c60% of glioma cases were mutants, while no mutation was found in the BC cohort. \u2018AA\u2019 and TT\u2019 were associated with higher disease risk (OR = 12.18 &amp; 4.68) in AML and had significantly upregulated IDH1 expression. Moreover, downregulated HIF1-\u03b1 and upregulated SIX-1 expression was also observed in these patients, suggesting that mutant-IDH1 may alter glucose metabolism. Perturbed IDH1 and HIF-\u03b1 levels exhibited poor prognosis in univariate and multivariate analysis, while age and gender were found to be contributory factors as well. Based on the ROC model, these had a good potential to be used as prognostic markers. A significant variation in frequencies of R132 mutations in AML among different populations was observed. Cytogenesis ( R\n                      <jats:sup>2<\/jats:sup>\n                      = 12.2%), NMP1 mutation status ( R\n                      <jats:sup>2<\/jats:sup>\n                      = 18.5%), and ethnic contributions ( R\n                      <jats:sup>2<\/jats:sup>\n                      = 73.21%) were critical moderators underlying these mutations. Women had a higher risk of R132 mutation (HR = 1.3, P &lt; 0.04). The pooled prevalence was calculated to be 0.29 (95% CI 0.26-0.33, P &lt; 0.01), indicating that IDH1 mutations are a significant prognostic factor in AML.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IDH1 and HIF1-\u03b1 profiles are linked to poor survival and prognosis, while high SIX-1 expression in IDH1 mutants suggests a role in leukemic transformation and therapy response in AML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10732748241271714","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T11:53:33Z","timestamp":1723031613000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Aberrant HIF1- \u03b1 and SIX-1 Expression is Associated with Poor Prognosis in Acute Myeloid Leukemia Patients with Isocitrate Dehydrogenase 1 Mutations"],"prefix":"10.1177","volume":"31","author":[{"given":"Tariq","family":"Ali","sequence":"first","affiliation":[{"name":"Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohma","family":"Usman","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Alasar","family":"Shah","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamir","family":"Parvez","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Summayya","family":"Anwar","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahid","family":"Muneer","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5998-787X","authenticated-orcid":false,"given":"Muhammad","family":"Saeed","sequence":"additional","affiliation":[{"name":"Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, 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