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The hypothesis of this study aimed to elucidate the relationship of HIF1\u03b1 with the redox system, Krebs cycles, notch1, and other regulatory proteins to better understand the pathophysiology and clinical relevance in chronic myeloid leukemia (CML) patients, as the molecular mechanism of this axis is still not clear. This study included CML patient samples (n = 60; 60: blood; 10: bone marrow tissues) and compared them with healthy controls (n = 20; blood). Clinical diagnosis confirmed on bone marrow aspiration, marrow trephine biopsy, and BCR\/ABL1 translocation. Cases were subclassified into chronic, accelerated, and blast crises as per WHO guidelines. Molecular experiments included redox parameters, DNA fragmentation, Krebs cycle metabolites, and gene expression by RT-PCR\/Western blot\/LC-MS, PPI (STRING), Pearson correlation, and ROC curve analysis. Here, our findings show that p210\/p190BCR\/ABL1 translocation is common in all blast crisis phases of CML. Redox factor\/Krebs oncometabolite concentrations were high, leading to upregulation and stabilization of HIF1\u03b1. HIF1\u03b1 leads to the pathogenesis in CML cells by upregulating their downstream genes (Notch 2\/4\/Ikaros\/SIRT1\/Foxo-3a\/p53, etc.). Whereas, downregulated ubiquitin proteasomal and apoptotic factors in CML pateints, can trigger degradation of HIF1\u03b1 through proline hydroxylation. However, HIF1\u03b1 showed a negative corelation with the notch1 pathway. Notch1 plays a tumor-suppressive role in CML and might have the potential to be used as a diagnostic marker along with other factors in CML patients. The outcome also revealed that oxidant treatment could not be effective in augmentation with conventional therapy because CML cells can enhance the levels of antioxidants for their survival. HIF1\u03b1 might be a novel therapeutic target other than BCR\/ABL1 translocation.<\/jats:p>","DOI":"10.3389\/fonc.2022.912942","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T05:54:37Z","timestamp":1656568477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The Molecular Role of HIF1\u03b1 Is Elucidated in Chronic Myeloid Leukemia"],"prefix":"10.3389","volume":"12","author":[{"given":"Vivek","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranjana","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashmi","family":"Kushwaha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailendra 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