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Asparaginase

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https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#1
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28628558/genetics-of-pleiotropic-effects-of-dexamethasone
#2
Laura B Ramsey, Stan Pounds, Cheng Cheng, Xueyuan Cao, Wenjian Yang, Colton Smith, Seth E Karol, Chengcheng Liu, John C Panetta, Hiroto Inaba, Jeffrey E Rubnitz, Monika L Metzger, Raul C Ribeiro, John T Sandlund, Sima Jeha, Ching-Hon Pui, William E Evans, Mary V Relling
OBJECTIVES: Glucocorticoids such as dexamethasone have pleiotropic effects, including desired antileukemic, anti-inflammatory, or immunosuppressive effects, and undesired metabolic or toxic effects. The most serious adverse effects of dexamethasone among patients with acute lymphoblastic leukemia are osteonecrosis and thrombosis. To identify inherited genomic variation involved in these severe adverse effects, we carried out genome-wide association studies (GWAS) by analyzing 14 pleiotropic glucocorticoid phenotypes in 391 patients with acute lymphoblastic leukemia...
June 16, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28622171/reactions-to-cytostatic-agents-in-children
#3
Josefina R Cernadas
PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug...
June 14, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28621166/l-asparaginase-for-newly-diagnosed-extra-nodal-nk-t-cell-lymphoma-systematic-review-and-meta-analysis
#4
Vadim S Pokrovsky, Denis Vinnikov
OBJECTIVES: The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients. METHODS: The PRISMA protocol was used to search PubMed and Embase for both controlled and uncontrolled studies of ASP or alternative chemotherapy (CT) for newly diagnosed ENKTL, published in English by March 2017. The regimens were compared to calculate relative risk (RR) with 95% confidence interval (CI) of the overall response rate (ORR), complete response (CR) or partial response (PR)...
June 21, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28602129/from-the-children-s-oncology-group-evidence-based-recommendations-for-peg-asparaginase-nurse-monitoring-hypersensitivity-reaction-management-and-patient-family-education
#5
Deborah Woods, Kari Winchester, Alison Towerman, Katie Gettinger, Christina Carey, Karen Timmermann, Rachel Langley, Emily Browne
PEG-aspariginase is a backbone chemotherapy agent in pediatric acute lymphoblastic leukemia and in some non-Hodgkin lymphoma therapies. Nurses lack standardized guidelines for monitoring patients receiving PEG-asparaginase and for educating patients/families about hypersensitivity reaction risks. An electronic search of 6 databases using publication years 2000-2015 and multiple professional organizations and clinical resources was conducted. Evidence sources were reviewed for topic applicability. Each of the final 23 sources was appraised by 2 team members...
June 1, 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28596278/hla-drb1-07-01-hla-dqa1-02-01-hla-dqb1-02-02-haplotype-is-associated-with-a-high-risk-of-asparaginase-hypersensitivity-in-acute-lymphoblastic-leukemia
#6
Nóra Kutszegi, Xiaoqin Yang, András Gézsi, Géza Schermann, Dániel J Erdélyi, Ágnes F Semsei, Krisztina M Gábor, Judit C Sági, Gábor T Kovács, András Falus, Hongyun Zhang, Csaba Szalai
Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian acute lymphoblastic leukemia population. Four-digit typing of HLA-DRB1 and HLA-DQB1 loci was performed in 359 pediatric acute lymphoblastic leukemia patients by using next-generation sequencing method...
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28596071/genetic-and-metabolic-engineering-approaches-for-the-production-and-delivery-of-l-asparaginases-an-overview
#7
REVIEW
Jalaja Vidya, Syed Sajitha, Mrudula Vasudevan Ushasree, Raveendran Sindhu, Parameswaran Binod, Aravind Madhavan, Ashok Pandey
L-asparaginase is one of the protein drugs for countering leukemia and lymphoma. A major challenge in the therapeutic potential of the enzyme is its immunogenicity, low-plasma half-life and glutaminase activity that are found to be the reasons for toxicities attributed to asparaginase therapy. For addressing these challenges, several research and developmental activities are going on throughout the world for an effective drug delivery for treatment of cancer. Hence there is an urgent need for the development of asparaginase with improved properties for efficient drug delivery...
May 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28588188/a-young-boy-with-l-asparaginase-induced-seizure
#8
M A Aziz, N K Singh, M H Rahman, M R Khan, A L Kabir, M Begum
L-Asparaginase is a critical component in the treatment of acute lymphoblastic leukemia in children. It is known to cause coagulation abnormalities, thrombosis and hemorrhage in the central nervous system in addition to vasculitis and hypersensitivity reactions. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Seizures are uncommon symptoms. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebrovascular events, completed in the department of Hematology of Bangabandhu Sheikh Mujib Medical University during March & April 2016...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28574850/whole-exome-sequencing-identified-genetic-risk-factors-for-asparaginase-related-complications-in-childhood-all-patients
#9
Rachid Abaji, Vincent Gagné, Chang Jiang Xu, Jean-François Spinella, Francesco Ceppi, Caroline Laverdière, Jean-Marie Leclerc, Stephen E Sallan, Donna Neuberg, Jeffery L Kutok, Lewis B Silverman, Daniel Sinnett, Maja Krajinovic
Allergy, pancreatitis and thrombosis are common side-effects of childhood acute lymphoblastic leukemia (ALL) treatment that are associated with the use of asparaginase (ASNase), a key component in most ALL treatment protocols. Starting with predicted functional germline variants obtained through whole-exome sequencing (WES) data of the Quebec childhood ALL cohort we performed exome-wide association studies with ASNase-related toxicities. A subset of top-ranking variants was further confirmed by genotyping (N=302) followed by validation in an independent replication group (N=282); except for thrombosis which was not available for that dataset...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28552244/ca-2-signalling-underlying-pancreatitis
#10
REVIEW
J V Gerasimenko, S Peng, T Tsugorka, O V Gerasimenko
In spite of significant scientific progress in recent years, acute pancreatitis (AP) is still a dangerous and in up to 5% of cases deadly disease with no specific cure. It is self-resolved in the majority of cases, but could result in chronic pancreatitis (CP) and increased risk of pancreatic cancer (PC). One of the early events in AP is premature activation of digestive pro-enzymes, including trypsinogen, inside pancreatic acinar cells (PACs) due to an excessive rise in the cytosolic Ca(2+) concentration, which is the result of Ca(2+) release from internal stores followed by Ca(2+) entry through the store operated Ca(2+) channels in the plasma membrane...
May 18, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28542249/the-human-asparaginase-enzyme-aspg-inhibits-growth-in-leukemic-cells
#11
Stefania Belviso, Rodolfo Iuliano, Rosario Amato, Nicola Perrotti, Miranda Menniti
The human protein ASPG is an enzyme with a putative antitumor activity. We generated in bacteria and then purified a recombinant GST-ASPG protein that we used to characterize the biochemical and cytotoxic properties of the human ASPG. We demonstrated that ASPG possesses asparaginase and PAF acetylhydrolase activities that depend on a critical threonine residue at position 19. Consistently, ASPG but not its T19A mutant showed cytotoxic activity in K562, NALM-6 and MOLT-4 leukemic cell lines but not in normal cells...
2017: PloS One
https://www.readbyqxmd.com/read/28523950/levocarnitine-and-vitamin-b-complex-for-the-treatment-of-pegaspargase-induced-hepatotoxicity-a-case-report-and-review-of-the-literature
#12
Alison Blackman, Alyssa Boutin, Alexei Shimanovsky, William J Baker, Nicholas Forcello
Asparaginase is a chemotherapeutic agent that is commonly used in combination with other medications for the treatment of acute lymphoblastic leukemia. An adverse effect of asparaginase includes hepatotoxicity, which can lead to severe liver failure and death. Several reports have documented successful treatment of asparaginase-induced hepatotoxicity using levocarnitine (l-carnitine) and vitamin B complex. Herein, we report a patient with acute lymphoblastic leukemia that experienced acute liver injury following pegaspargase administration...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28505420/immobilization-of-l-asparaginase-on-carrier-materials-a-comprehensive-review
#13
Ahmet Ulu, Burhan Ates
There are two major applications of l-asparaginase (L-ASNase): leukemia therapy and the food industry. Especially, its chemotherapeutic effect has attracted interest from the scientific community and individual scientists. Therefore, to protect the intrinsic activity and half-time of L-ASNase, several carriers and immobilization techniques for immobilization of L-ASNase have been described in articles. Unfortunately, a comprehensive review about immobilization of L-ASNase has not been written until now. In this review, we have thoroughly discussed the carriers for L-ASNase by illustrating immobilization findings including both past and present applications...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28503810/a-minor-role-of-asparaginase-in-predisposing-to-cerebral-venous-thromboses-in-adult-acute-lymphoblastic-leukemia-patients
#14
Saara Roininen, Outi Laine, Marjut Kauppila, Marko Vesanen, Maria Rämet, Marjatta Sinisalo, Esa Jantunen, Marjaana Säily, Riikka Räty, Erkki Elonen, Ulla Wartiovaara-Kautto
Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000...
June 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28497204/the-biology-and-the-importance-of-photobacterium-species
#15
REVIEW
Ibrahim Musa Moi, Noordiyanah Nadhirah Roslan, Adam Thean Chor Leow, Mohd Shukuri Mohamad Ali, Raja Noor Zaliha Raja Abd Rahman, Azam Rahimpour, Suriana Sabri
Photobacterium species are Gram-negative coccobacilli which are distributed in marine habitats worldwide. Some species are unique because of their capability to produce luminescence. Taxonomically, about 23 species and 2 subspecies are validated to date. Genomes from a few Photobacterium spp. have been sequenced and studied. They are considered a special group of bacteria because some species are capable of producing essential polyunsaturated fatty acids, antibacterial compounds, lipases, esterases and asparaginases...
May 11, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28486976/tropicall-study-thromboprophylaxis-in-children-treated-for-acute-lymphoblastic-leukemia-with-low-molecular-weight-heparin-a-multicenter-randomized-controlled-trial
#16
Irene L M Klaassen, Mandy N Lauw, Marianne D van de Wetering, Bart J Biemond, Saskia Middeldorp, Floor C H Abbink, Marc Bierings, D Maroeska M W Te Loo, Rob Pieters, Inge M van der Sluis, Wim J E Tissing, C Michel Zwaan, C Heleen van Ommen
BACKGROUND: Venous thromboembolism (VTE) is a common and severe complication during treatment of acute lymphoblastic leukemia (ALL). An important cause is the intensive use of asparaginase. Prospective cohort studies in which prophylactic low-molecular-weight heparin (LMWH) was used to prevent VTE showed lower VTE risk than in historic control cohorts, with a negligible bleeding risk. However, the efficacy of thromboprophylaxis with LMWH during ALL treatment has never been investigated in a randomized design...
May 10, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28482728/safety-and-feasibility-of-lower-antithrombin-replacement-targets-in-adult-patients-with-hematological-malignancies-receiving-asparaginase-therapy
#17
Jason N Barreto, Kristen B McCullough, Candy S Peskey, Ross A Dierkhising, Kristin C Mara, Michelle A Elliott, Dennis A Gastineau, Aref Al-Kali, Naseema Gangat, Louis Letendre, William J Hogan, Mark R Litzow, Mrinal M Patnaik
The optimal antithrombin(AT) activity parameters for replacement as thromboprophylaxis following asparaginase remains unclear. This single-center, retrospective study evaluated two sets of AT replacement thresholds and targets in adults receiving asparaginase-containing chemotherapy. AT supplementation adhered to institutional standards, which lowered the AT activity target from 100% to 80% in 6/2014. Ninety-two patients were evaluated. Cumulative thrombosis incidence was 16% at 6 months (95%CI:6.8-24.0, maximum follow-up 315 days) with similar incidence between the 80% and 100% target groups, 14% (2 of the 14) and 13% (10 of the 78), respectively, with a small non-Line-Related DVT incidence (3%)...
May 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28472942/evaluation-for-inherited-and-acquired-prothrombotic-defects-predisposing-to-symptomatic-thromboembolism-in-children-with-acute-lymphoblastic-leukemia-a-protocol-for-a-prospective-observational-cohort-study
#18
Uma H Athale, Caroline Laverdiere, Trishana Nayiager, Yves-Line Delva, Gary Foster, Lehana Thabane, Anthony Kc Chan
BACKGROUND: Thromboembolism (TE) is a serious complication in children with acute lymphoblastic leukemia (ALL). The incidence of symptomatic thromboembolism is as high as 14% and case fatality rate of ~15%. Further, development of thromboembolism interferes with the scheduled chemotherapy with potential impact on cure rates. The exact pathogenesis of ALL-associated thromboembolism is unknown. Concomitant administration of asparaginase and steroids, two important anti-leukemic agents, is shown to increase the risk of ALL-associated TE...
May 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28461187/hyperthermophilic-l-asparaginase-bypasses-monomeric-intermediates-during-folding-to-retain-cooperativity-and-avoid-amyloid-assembly
#19
Dushyant K Garg, Bishwajit Kundu
In obligate dimeric proteins of hyperthermophilic origin the question whether the native dimer is obtained by association of folded monomers or through concomitant folding and assembly of subunits has intrigued researchers. To find an answer we studied the folding of a dimeric enzyme l-asparaginase from Pyrococcus furiosus (PfA) for which we reported earlier that it unfolds cooperatively without populating folded monomeric intermediates. However, in the present study we report the finding of a folded monomeric intermediate of PfA under acidic condition...
May 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28455513/role-of-activating-transcription-factor-4-in-the-hepatic-response-to-amino-acid-depletion-by-asparaginase
#20
Rana J T Al-Baghdadi, Inna A Nikonorova, Emily T Mirek, Yongping Wang, Jinhee Park, William J Belden, Ronald C Wek, Tracy G Anthony
The anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2 (-/-), and Atf4 (-/-) mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4 (+/-) mice...
April 28, 2017: Scientific Reports
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