High Mitophagy and Low Glycolysis Predict Better Clinical Outcomes in Acute Myeloid Leukemias DOI Open Access
Amreen Salwa, Alessandra Ferraresi, Letizia Vallino

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11527 - 11527

Published: Oct. 27, 2024

Acute myeloid leukemia (AML) emerges as one of the most common and fatal leukemias. Treatment disease remains highly challenging owing to profound metabolic rewiring mechanisms that confer plasticity AML cells, ultimately resulting in therapy resistance. Autophagy, a conserved lysosomal-driven catabolic process devoted macromolecular turnover, displays dichotomous role by suppressing or promoting development progression. Glycolytic metabolism represents pivotal strategy for cells sustain increasing energy needs related uncontrolled growth during In this study, we tested hypothesis high glycolytic rate low autophagy flux could represent an advantage cell proliferation thus be detrimental patient’s prognosis, vice versa. TCGA silico analysis cohort shows expression MAP1LC3B (along with BECN1 p62/SQSTM1) BNIP3 PRKN MAP1LC3B), which together are indicative increased mitophagy, correlate better prognosis. On other hand, markers HK2, PFKM, PKM correlates poor Most importantly, association autophagy–mitophagy conferred longest overall survival patients. Transcriptomic showed combined signature downregulation subset genes required differentiation lactate/pyruvate transporters, cycle progression, parallel upregulation involved autophagy/lysosomal trafficking proteolysis, anti-tumor responses like beta-interferon production, positive regulation programmed death. Taken together, our data support view enhanced autophagy-mitophagy predisposes patients clinical outcome, suggesting inducers glucose restrictors may hold potential adjuvant therapeutics improving management.

Language: Английский

Function of intramitochondrial melatonin and its association with Warburg metabolism DOI Creative Commons

R.J. Reiter,

Ramaswamy Sharma, Yidong Bai

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111754 - 111754

Published: March 1, 2025

Language: Английский

Citations

1
Identifying acute myeloid leukemia subtypes based on pathway enrichment DOI Creative Commons
Ling Zhong,

Jiangti Luo,

Junze Dong

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Acute myeloid leukemia (AML) is the most common type of acute in adults and second children. Despite introduction targeted therapies, AML survival rates have shown limited improvement, particularly among older patients. This study explored personalized treatment strategies for by proposing a novel subtyping method. Through unsupervised clustering based on enrichment scores 14 pathways related to metabolism, immunity, DNA repair, oncogenic signaling, we identified three subtypes: repair (DR), immune-enriched (ImE), immune-deprived (ImD), consistent four independent datasets. DR marked high expression metabolic pathways, stemness proliferation potential, as well sensitivity chemotherapy. ImD characterized low immune favorable prognosis, mutation RUNX1 TP53 , homeostasis, migration potential. ImE exhibits capacity, Our pathway enrichment-based approach would offer promising framework understanding molecular heterogeneity guiding this disease.

Language: Английский

Citations

0
Lactate dehydrogenase A-coupled NAD+ regeneration is critical for acute myeloid leukemia cell survival DOI Creative Commons

Ayşegül Erdem,

S.B. Kaye,

Francesco Caligiore

et al.

Cancer & Metabolism, Journal Year: 2025, Volume and Issue: 13(1)

Published: May 19, 2025

Language: Английский

Citations

0
Impact of physiological media on acute myeloid leukemia bioenergetics and cell proliferation DOI Creative Commons
Brett R Chrest, McLane M. Montgomery, Raphael Taiwo Aruleba

et al.

Cancer & Metabolism, Journal Year: 2025, Volume and Issue: 13(1)

Published: May 26, 2025

Increasing emphasis has been placed on improving the physiological relevance of cell culture media with formulations such as Human Plasma-Like Medium (HPLM). Given that shifts in mitochondrial metabolism and nutrient use are emerging anti-cancer targets, present study sought to investigate impact formulation bioenergetics cancer growth. To do this, we used acute myeloid leukemia (AML) cells compared chronic effects HPLM versus different supraphysiological medias. The AML phenotype was largely unaffected by exposure either or medias, establishing key features mitochondria remain phenotypically stable under diverse conditions proliferation rates. Both culturing slowed proliferation. However, merely identifying supplementing single nutrients were deficient did not improve sufficient pinpoint actionable fuel preferences. Transferring back native Iscove's Modified Dulbecco's (IMDM) immediately restored proliferative phenotype, suggesting responsiveness entirety environment. Supraphysiological medias other than IMDM all characterized slower proliferation; however, none associated changes viability, demonstrating medium is optimal if experimental aim maximal Despite Eagle (DMEM) being similar composition categorized supraphysiological, both DMEM resulted growth, akin what observed HPLM. Altogether, independent unperturbed media, rather specific relevance, influenced complete profile.

Language: Английский

Citations

0
Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions DOI Open Access
Martina Maria Capelletti,

Orsola Montini,

Emilio Ruini

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 45 - 45

Published: Dec. 24, 2024

Genetic studies of haematological cancers have pointed out the heterogeneity leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting treatment response. Next-generation sequencing (NGS) genome-wide analyses, as well single-cell technologies, offered unprecedented insights into clonal within same tumour. A key component this that remains unexplored is intracellular metabolome, a dynamic network determines cell functions, signalling, epigenome regulation, immunity inflammation. Understanding metabolic diversities among cancer cells their surrounding environments therefore essential unravelling complexities improving therapeutic strategies. Here, we describe currently available methodologies approaches to addressing progression. In second section, focus on leukaemic vulnerabilities acute myeloid (AML) lymphoblastic (ALL). Lastly, provide comprehensive overview most interesting clinical trials designed target these dependencies, highlighting potential advance strategies treatment. The integration multi-omics data for identification states tumour will enable “micro-to-macro” approach refinement practices delivery personalised therapies.

Language: Английский

Citations

0
High Mitophagy and Low Glycolysis Predict Better Clinical Outcomes in Acute Myeloid Leukemias DOI Open Access
Amreen Salwa, Alessandra Ferraresi, Letizia Vallino

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11527 - 11527

Published: Oct. 27, 2024

Acute myeloid leukemia (AML) emerges as one of the most common and fatal leukemias. Treatment disease remains highly challenging owing to profound metabolic rewiring mechanisms that confer plasticity AML cells, ultimately resulting in therapy resistance. Autophagy, a conserved lysosomal-driven catabolic process devoted macromolecular turnover, displays dichotomous role by suppressing or promoting development progression. Glycolytic metabolism represents pivotal strategy for cells sustain increasing energy needs related uncontrolled growth during In this study, we tested hypothesis high glycolytic rate low autophagy flux could represent an advantage cell proliferation thus be detrimental patient’s prognosis, vice versa. TCGA silico analysis cohort shows expression MAP1LC3B (along with BECN1 p62/SQSTM1) BNIP3 PRKN MAP1LC3B), which together are indicative increased mitophagy, correlate better prognosis. On other hand, markers HK2, PFKM, PKM correlates poor Most importantly, association autophagy–mitophagy conferred longest overall survival patients. Transcriptomic showed combined signature downregulation subset genes required differentiation lactate/pyruvate transporters, cycle progression, parallel upregulation involved autophagy/lysosomal trafficking proteolysis, anti-tumor responses like beta-interferon production, positive regulation programmed death. Taken together, our data support view enhanced autophagy-mitophagy predisposes patients clinical outcome, suggesting inducers glucose restrictors may hold potential adjuvant therapeutics improving management.

Language: Английский

Citations

0