Catalyzing improvements in ALL therapy with asparaginase

Marini, Bernard L.; Perissinotti, Anthony J.; Bixby, Dale; Brown, Julia; Burke, Patrick W.

doi:10.1016/j.blre.2017.06.002

Cited by 40 publications

(29 citation statements)

References 61 publications

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“…Studies in animals indicated that changes of pyrimidine metabolism with increased hepatic lipid [36,37]. Asparagine is a non-essential amino acid in normal cells, as cells are able to synthesize asparagine from other amino acid, such as glutamate/glutamine and aspartate, though transaminases and asparagine synthetase [38]. Studies suggested that depletion of asparagine was associated with improved outcomes in ALI [38].…”

Section: Discussionmentioning

confidence: 99%

Changes of microbiota and metabolome of the equine hindgut during oligofructose-induced laminitis

Tuniyazi

Guo

et al. 2020

Preprint

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Background: Laminitis is a common but serve conditions caused by inflammatory and pathologic changes of the laminar junction. However, the pathologic mechanism remains unclear. In this study we aimed to investigate changes of the gut microbiota and metabolomics in oligofructose-induced laminitis of horses. Results: Treatment with oligofructose had lower fecal pH but higher lactic acid, histamine, and Lipopolysaccharide (LPS) in serum. Meanwhile, oligofructose altered composition of the hindgut bacterial community, demonstrated by increasing relative abundance of Lactobacollus and Megasphaere. In addition, the metabolome analysis revealed that treatment of oligofructose decreased 84 metabolites while 53 metabolites increased, such as dihydrothymine, N3,N4-Dimethyl-L-arginine, 10E,12Z-Octadecadienoic acid, and asparagine. Pathway analysis revealed that aldosterone synthesis and secretion, regulation of lipolysis in adipocytes, steroid hormone biosynthesis, pyrimidine metabolism, biosynthesis of unsaturated fatty acids, and galactose metabolism were significantly different between healthy and laminitis horses. Furthermore, correlation analysis between gut microbiota and metabolites indicated that Lactobacillus and/or Megasphaera were positively associated with the dihydrothymine, N3,N4-Dimethyl-L-arginine, 10E,12Z-Octadecadienoic acid, and asparagine. Conclusions: These results revealed that disturbance of gut microbiota and changes of metabolites were occurred during the development of equine laminitis, and these results may provide novel insights to detect biomarkers for a better understanding of the potential mechanism and prevention strategies for laminitis in horses.

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Section: Discussionmentioning

confidence: 99%

Changes of microbiota and metabolome of the equine hindgut during oligofructose-induced laminitis

Tuniyazi

Guo

et al. 2020

Preprint

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“…94 A sharp reduction of the cellular Asn pool using ASNase, which hydrolyzes the Asn amide to generate aspartate and ammonia, sufficiently retards mRNA translation to ultimately induce apoptosis in ALL cells. 95 in patients under age 35, but no change in outcomes measured by metrics such as remission rate and survival time. 96 The occurrence and the intensity of side effects measured (such as liver and kidney damage) were also comparable between the two ASNase forms.…”

Section: Figurementioning

confidence: 94%

“…It has been known for a half century that asparagine (Asn), normally a nonessential amino acid, is essential to ALL cells due to deficient activity of asparagine synthetase . A sharp reduction of the cellular Asn pool using ASNase, which hydrolyzes the Asn amide to generate aspartate and ammonia, sufficiently retards mRNA translation to ultimately induce apoptosis in ALL cells . Unfortunately, although ALL cells are particularly reliant on Asn, cross‐reactivity of ASNase with other cell types results in significant side effects to an extent that has limited the use of ASNase in adult ALL cases.…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

“…96 The occurrence and the intensity of side effects measured (such as liver and kidney damage) were also comparable between the two ASNase forms. 96 Resistance to ASNase therapy can occur through several mechanisms; from a metabolic standpoint, glutamine/glutamate metabolism has attracted attention as these can also serve as precursors for Asn (see Marini et al 95 for a recent review on asparaginase therapy in ALL).…”

Section: Figurementioning

confidence: 99%

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Metabolic underpinnings of leukemia pathology and treatment

2018

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Background Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a disruption of normal bone marrow function. Leukemias are diverse in type, affected population, prognosis, and treatment regimen, yet a common theme in leukemia is the dysregulated metabolism of leukemic cells and leukemic stem cells with respect to their noncancerous counterparts. Recent findings In this review, we highlight current findings that elucidate metabolic traits unique to the four major types of leukemia, which confer carcinogenic survival but can be potentially exploited for therapeutic intervention. These metabolic features can work in conjunction with or be independent of unique aspects of the bone marrow microenvironment that can also influence cell survival and proliferation, thus sustaining carcinogenesis. Conclusion Deepening our understanding of the interactions of leukemias with their niche environments in vivo will inform future treatments for leukemia, particularly for those that are refractive to tyrosine kinase inhibitors and other therapeutic mainstays.

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“…Em células humanas normais, a asparagina é um aminoácido não essencial, já que pode ser sintetizada a partir de outros aminoácidos (como glutamato, glutamina e aspartato), através de transaminases e asparagina sintetase (MARINI et al, 2017). O modo de ação da enzima L-ASNase consiste no fato das células leucêmicas necessitarem de elevadas quantidades do aminoácido L-asparagina para a sua proliferação, além de não o sintetizarem em quantidades suficientes em razão de baixa ou nenhuma capacidade de produção de asparagina sintetase (NARTA et al, 2007; RAETZ; SALZER, 2010; KUMAR; SOBHA, 2012).…”

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Produção de L-asparaginase pela levedura >i<Leucosporidium muscorum>/i< CRM 1648 isolada de sedimento marinho coletado na Península Antártica

Freire¹

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Como ligar 9 pontos utilizando apenas 4 linhas retas? Quando olhamos a figura e temos um olhar mais rígido, tendenciamos a limitar-nos à imagem do quadrado formado pelos pontos. Esse olhar fixo, limitado, faz a gente não alcançar a solução do problema que é, justamente, OLHAR PARA FORA, sair dos limites, ir além. Para fazer Ciência é preciso "sair da caixa", para fazer Ciência é preciso "pensar vivo" e o conhecimento vivo é aquele que nunca se fecha, pois o final representa sempre o começo de um novo pensar. Rominne Freire (trecho do portfólio desenvolvido como parte do curso livre de Pedagogia Waldorf, em Fevereiro de 2017). "A coisa mais bela que podemos experimentar é o mistério. Essa é a fonte de toda a arte e ciências verdadeiras".

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Catalyzing improvements in ALL therapy with asparaginase

Cited by 40 publications

References 61 publications

Changes of microbiota and metabolome of the equine hindgut during oligofructose-induced laminitis

Changes of microbiota and metabolome of the equine hindgut during oligofructose-induced laminitis

Metabolic underpinnings of leukemia pathology and treatment

Produção de L-asparaginase pela levedura >i<Leucosporidium muscorum>/i< CRM 1648 isolada de sedimento marinho coletado na Península Antártica

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