Accelerated, untargeted metabolomics analysis of cutaneous T‐cell lymphoma reveals metabolic shifts in plasma and tumor adjacent skins of xenograft mice

Le, Yunchen; Shen, X. Y.; Kang, Hongyan; Wang, Qizheng; Li, Kejia; Jiao, Z.; Yu, Yunqiu

doi:10.1002/jms.4207

Cited by 5 publications

(4 citation statements)

References 1 publication

(1 reference statement)

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“…In cutaneous T-cell lymphoma (CTCL), a class of NHL, and a heterogeneous group of skin-homing Tcell neoplasms, ultrahigh performance liquid chromatographyquadrupole (UHPLC-Q) TOF/MS and further LC/MS-MS determined the 36 potential biomarkers associated with CTCL, which are derived from CTCL plasma metabolic perturbations (36). In skin and plasma of CTCL mice, UHPLC-QTOF/MS also demonstrate that increased Lglutamate and decreased adenosine monophosphate are the most essential metabolic pathways of CTCL tumors and tumor adjacent skins (37). Data from GC-MS and UHPLC-QTOF/MS show that glycerophospholipid metabolism, tryptophan metabolism, and purine metabolism are altered pathways in serum samples from 31 patients with CTCL (38).…”

Section: Discussionmentioning

confidence: 99%

Metabolome analysis reveals excessive glycolysis via PI3K/AKT/mTOR and RAS/MAPK signaling in methotrexate-resistant primary CNS lymphoma-derived cells

Takashima

Hayano

2020

Clin Cancer Res

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Purpose: Metabolome analysis is an emerging method that provides insight into intracellular and physiologic responses. Methotrexate (MTX) is an antifolate that suppresses DNA syntheses by inhibiting dihydrofolate reductase. High-dose methotrexate treatment with deferred radiotherapy is a standard protocol in primary central nervous system lymphoma (PCNSL) treatments. However, most cases come to relapse-acquired resistance, in which the role of metabolic pathways is largely unknown.Experimental Design: Metabolome analysis in methotrexateresistant PCNSL-derived cells (designated as TK-MTX and HKBML-MTX) was performed to detect alternative metabolites and pathways.Results: The metabolomic analyses using capillary electrophoresis-time-of-flight mass spectrometry detected 188 and 169 peaks in TK-and HKBML-derived cells, respectively, including suppression of central carbon metabolism, lipid metabolism, nucleic acid metabolism, urea cycle, branched chain and aromatic amino acids, and coenzyme metabolism. Particularly, whole suppressive metabolic pathways were demonstrated in TK-MTX, whereas HKBML-MTX indicated partially enhanced pathways of the urea cycle, amino acid metabolism, and coenzyme metabolism. Reciprocally detected metabolites for glycolysis, including induced glucose and reduced glycogen, and induced lactate and reduced pyruvate, in addition to increased lactate dehydrogenase activity, which is involved in Warburg effect. Thereby, ATP was increased in both methotrexate-resistant PCNSL-derived cells. Furthermore, we specifically found that PI3K/AKT/mTOR and RAS/MAPK signaling pathways were activated in TK-MTX but not in HKBML-MTX by growth rate with inhibitors and gene expression analysis, suggestive of cell type-specific methotrexate-resistant metabolic pathways.Conclusions: These results can help us understand targeted therapies with selective anticancer drugs in recurrent CNS lymphoma-acquired resistance against methotrexate.

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Section: Discussionmentioning

confidence: 99%

Metabolome analysis reveals excessive glycolysis via PI3K/AKT/mTOR and RAS/MAPK signaling in methotrexate-resistant primary CNS lymphoma-derived cells

Takashima

Hayano

2020

Clin Cancer Res

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“…Serum metabolomics analysis can identify high-risk DLBCL patients with failure of immunochemotherapy, which might provide another novel, non-invasive way for the diagnosis and prognosis of lymphoma [ 254 ]. A study on the skin and plasma of CTCL mice indicated that aberrant metabolites and metabolic pathways were essential metabolic features of CTCLs, whereas accumulative cytidine-5′-triphosphate in adjacent non-involved skin tissues led to CTCL further development [ 255 ]. Changes in lipid profiles provide new biological insights into how MYC regulates cellular metabolism in MYC-induced lymphoma [ 256 ] ( Table 4 ).…”

Section: Potential Metabolic Biomarkers Of Lymphomamentioning

confidence: 99%

Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma

Pang

Xu-Monette

et al. 2023

IJMS

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Lymphoma is a heterogeneous group of diseases that often require their metabolism program to fulfill the demand of cell proliferation. Features of metabolism in lymphoma cells include high glucose uptake, deregulated expression of enzymes related to glycolysis, dual capacity for glycolytic and oxidative metabolism, elevated glutamine metabolism, and fatty acid synthesis. These aberrant metabolic changes lead to tumorigenesis, disease progression, and resistance to lymphoma chemotherapy. This metabolic reprogramming, including glucose, nucleic acid, fatty acid, and amino acid metabolism, is a dynamic process caused not only by genetic and epigenetic changes, but also by changes in the microenvironment affected by viral infections. Notably, some critical metabolic enzymes and metabolites may play vital roles in lymphomagenesis and progression. Recent studies have uncovered that metabolic pathways might have clinical impacts on the diagnosis, characterization, and treatment of lymphoma subtypes. However, determining the clinical relevance of biomarkers and therapeutic targets related to lymphoma metabolism is still challenging. In this review, we systematically summarize current studies on metabolism reprogramming in lymphoma, and we mainly focus on disorders of glucose, amino acids, and lipid metabolisms, as well as dysregulation of molecules in metabolic pathways, oncometabolites, and potential metabolic biomarkers. We then discuss strategies directly or indirectly for those potential therapeutic targets. Finally, we prospect the future directions of lymphoma treatment on metabolic reprogramming.

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“…UHPLC-MS analysis was conducted on a 1290 In nity UHPLC system coupled to a 6530 iFunnel ESI-Q-TOF mass spectrometer (Agilent Technologies, CA, USA) that was equipped with a degasser, binary pump and thermostatically controlled autosampler. Chromatographic separation was carried out on an ACQUITY UPLC HSS T3 column (2.1 mm x 100 mm, 1.8 μm, Milford, MA, USA) with 0.1% formic acid in either water (A) or acetonitrile (B) as the mobile phase [24,25]. The percentage of mobile phase A was kept at 99% for the rst 1 min and decreased linearly to 60%, 50% and 35% over the next 4 min, 3 min and 8 min, respectively, under a ow rate of 0.3 mL/min.…”

Section: Mass Spectrometrymentioning

confidence: 99%

Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients

Cao

Yang

et al. 2021

Preprint

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Background: Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear.Methods: Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases. Results: A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment.Conclusion: The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities.

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Accelerated, untargeted metabolomics analysis of cutaneous T‐cell lymphoma reveals metabolic shifts in plasma and tumor adjacent skins of xenograft mice

Cited by 5 publications

References 1 publication

Metabolome analysis reveals excessive glycolysis via PI3K/AKT/mTOR and RAS/MAPK signaling in methotrexate-resistant primary CNS lymphoma-derived cells

Metabolome analysis reveals excessive glycolysis via PI3K/AKT/mTOR and RAS/MAPK signaling in methotrexate-resistant primary CNS lymphoma-derived cells

Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma

Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients

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