Mitophagy-Driven Prognosis in Pediatric Acute Myeloid Leukemia: A New Frontier

Mitophagy-Driven Prognosis in Pediatric Acute Myeloid Leukemia: A New Frontier | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 16 April 2025 V1 Latest version Share on Mitophagy-Driven Prognosis in Pediatric Acute Myeloid Leukemia: A New Frontier Authors : Rajiv Ranjan Kumar 0000-0003-2750-1174 , Uttam Sharma 0000-0001-5108-8872 , Akshi Shree , Shilpi Chaudhary , Shuvadeep Ganguly 0000-0002-7296-6088 , Radhika Bakhshi , Archna Singh , Jayanth Kumar Palanichamy , and Sameer Bakhshi 0000-0001-9367-4407 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174479256.66064592/v1 Published Scientific Reports Version of record Peer review timeline 276 views 123 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Mitophagy is a crucial mitochondrial quality control mechanism that removes dysfunctional mitochondria via lysosomal degradation, maintaining cellular homeostasis. Cancer cells exploit this process to sustain mitochondrial function, promote tumor renewal, and enhance therapy resistance. While mitophagy has been extensively studied in solid tumors, its role in Acute Myeloid Leukemia (AML), particularly in pediatric cases, remains largely unexplored. Therefore, this study investigated the prognostic value of pivotal mitophagy-related genes, PINK1, FUNDC1, and BNIP3, contributing to the flagging and recognition of damaged mitochondria. Methodology: Expression of PINK1 , FUNDC1 , and BNIP3 was analyzed using qRT-PCR in bone marrow samples from 90 pediatric AML patients and 30 controls. Kaplan-Meier survival analysis was performed to evaluate their association with overall survival (OS) and relapse-free survival (RFS) based on quartile expression. Pathway enrichment analysis was conducted using bioinformatics tools. Results: PINK1 (fold-change ~2.5, p = 0.0180) and FUNDC1 (fold-change ~4.0, p = 0.0335) were significantly upregulated in AML samples, with lower quartile expression of PINK1 strongly correlating with poor overall survival (OS) [Hazard Ratio (HR) = 3.636; 95% Confidence Interval (CI): 1.723–7.671; p = 0.0001]. Similarly, the lower quartile expression of FUNDC1 was associated with poor OS (HR = 2.027; 95% CI: 0.9474–4.339; p = 0.0384). Notably, BNIP3 expression did not differ significantly between pediatric AML and control samples (p = 0.769); however, higher quartile expression of BNIP3 was associated with poorer OS (HR = 3.238; 95% CI: 1.500–6.989; p = 0.0001). We did not observe the association of mitophagy-related genes with RFS. Pathway enrichment analysis revealed that PINK1 and FUNDC1 play key roles in mitophagy and hypoxia adaptation, while BNIP3 is primarily involved in apoptosis and cellular stress signaling. Conclusion: Overall, PINK1 and FUNDC1 may be potential prognostic biomarkers for OS in pediatric AML, emphasizing their role in mitochondrial homeostasis and leukemia progression. However, BNIP3 could also be used as prognostic markers; further validation on a large sample size is still required. This study will open a new AML diagnosis, prognosis, and therapy frontier. Supplementary Material File (rrk- mitiophagy_03042025.docx) Download 102.56 KB Information & Authors Information Version history V1 Version 1 16 April 2025 Peer review timeline Published Scientific Reports Version of Record 3 Mar 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords "non-hodgkin"s...lymphoma" all all relapse alternative medicine aml bmt cml molecular biology of molecular diagnosis & therapy Authors Affiliations Rajiv Ranjan Kumar 0000-0003-2750-1174 All India Institute of Medical Sciences New Delhi View all articles by this author Uttam Sharma 0000-0001-5108-8872 All India Institute of Medical Sciences New Delhi View all articles by this author Akshi Shree All India Institute of Medical Sciences New Delhi View all articles by this author Shilpi Chaudhary New York-Presbyterian/Columbia University Irving Medical Center View all articles by this author Shuvadeep Ganguly 0000-0002-7296-6088 Jawaharlal Institute of Post Graduate Medical Education Department of Pediatrics View all articles by this author Radhika Bakhshi Shaheed Rajguru College of Applied Sciences for Women Department of Biomedical Science View all articles by this author Archna Singh All India Institute of Medical Sciences New Delhi View all articles by this author Jayanth Kumar Palanichamy All India Institute of Medical Sciences New Delhi View all articles by this author Sameer Bakhshi 0000-0001-9367-4407 [email protected] All India Institute of Medical Sciences New Delhi View all articles by this author Metrics & Citations Metrics Article Usage 276 views 123 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Rajiv Ranjan Kumar, Uttam Sharma, Akshi Shree, et al. Mitophagy-Driven Prognosis in Pediatric Acute Myeloid Leukemia: A New Frontier. Authorea . 16 April 2025. DOI: https://doi.org/10.22541/au.174479256.66064592/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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