- https://doi.org/10.18502/ajmb.v17i3.19275
Characterization and Evaluation of the Anti-proliferative Activity and Hypersensitivity of L-Asparaginase from Trichosporon asahii Isolate ChL11 and Candida palmioleophila Isolate JK12
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Take Notes Background: L-Asparaginase is a crucial enzyme to treat Acute Lymphoblastic Leukemia (ALL), as it depletes L-asparagine, an essential amino acid for cancer cell survival. However, its clinical use is often restricted due to hypersensitivity reactions. This study examined the anti-proliferative effects and hypersensitivity of fungal L-aspara-ginases (L-ASNases) from Trichosporon asahii isolate ChL11 (TaIChL11 L-ASNase) and Candida palmioleophila isolate JK12 (CpIJK12 L-ASNase). Methods: The enzymes were produced and purified through ammonium sulfate precipitation, dialysis, and Sephadex G-100 chromatography, and tested on leukemia cells and BALB/c female mice to assess immune responses. Results: TaIChL11 L-ASNase had a molecular weight of 40 kDa, Michaelis constant (KM) of 1.66×10⁻² mM, and Vmax of 37.23 mM/min, while CpIJK12 L-ASNase had a molecular weight of 135 kDa, KM of 2.3×10⁻² mM, and Vmax of 14.03 mM/min. Both enzymes exhibited significant anti-proliferative effects against CCRF-CEM cancer cells, with half-maximal inhibitory concentration (IC50) values of 2.74 U/ml for TaIChL11 L-ASNase and 3.30 U/ml for CpIJK12 L-ASNase after 48 hr, improving further after 72 hr. They also showed low cytotoxicity toward normal Vero E6 cells. in vivo studies demonstrated that TaIChL11 ASNase-treated mice had significantly lower Immunoglobulin (Ig) G levels than those treated with commercial L-ASNase from Erwinia chrysanthemi (Owenism) (p<0.005), with no detectable IgE response. Conclusion: These findings indicate that fungal L-ASNases, particularly TaIChL11 ASNase, with lower L-glutaminase activity and a favorable safety profile, could be promising alternatives to bacterial L-ASNases, potentially enhancing ALL treatment with fewer side effects.
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148 - 10.1046/j.1365-2141.2003.04393.x
- Jun 1, 2003
- British Journal of Haematology
Determination of minimal residual disease in leukaemia patients.
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- 92
- 10.1002/cyto.a.10104
- Feb 25, 2004
- Cytometry Part A
Alberto Orfao,* Francisco Ortuno, Maria de Santiago, Antonio Lopez, and Jesus San Miguel Servicio General de Citometria, Universidad de Salamanca, Salamanca, Spain Centro de Investigacion del Cancer y Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain Servicio de Hematologia y Oncologia Medica, Hospital General Universitario J.M. Morales Meseguer, Murcia, Spain Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain
- Research Article
- 35
- 10.1086/505645
- Aug 1, 2006
- The American Journal of Human Genetics
Epigenetic Regulation of Human γ-Glutamyl Hydrolase Activity in Acute Lymphoblastic Leukemia Cells
- Peer Review Report
- 10.7554/elife.83533.sa2
- Dec 21, 2022
Author response: Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling
- Peer Review Report
- 10.7554/elife.83533.sa1
- Nov 9, 2022
Decision letter: Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling
- Peer Review Report
- 10.7554/elife.83533.sa0
- Nov 9, 2022
Editor's evaluation: Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling
- Research Article
- 63
- 10.1016/j.exphem.2012.11.004
- Nov 22, 2012
- Experimental Hematology
Plerixafor (AMD3100) induces prolonged mobilization of acute lymphoblastic leukemia cells and increases the proportion of cycling cells in the blood in mice
- Abstract
- 10.1182/blood.v120.21.291.291
- Nov 16, 2012
- Blood
ITIM-Containing Inhibitory Receptors Are Required to Balance Oncogenic Signaling Strength in Ph+ ALL
- Research Article
- 12
- 10.3389/fphar.2021.607755
- May 28, 2021
- Frontiers in Pharmacology
Acute lymphoblastic leukemia (ALL) is an aggressive malignancy. Adults with ALL have more than 50% relapse rates. We have previously validated that overexpression of nucleophosmin (NPM) is involved in the multidrug resistance (MDR) development during ALL; and a synthetically engineered recombinant NPM binding protein (NPMBP) has been developed in our group; NPMBP and doxorubicin (DOX) can be conjugated in a nanoparticle-based drug delivery system named DOX-PMs-NPMBP to counteract MDR during ALL. Here, we evaluated the antileukemia potential of DOX-PMs-NPMBP in resistant ALL cells. This study demonstrates that DOX-PMs-NPMBP significantly enhances chemosensitivity to DOX in ALL cells. Despite at variable concentrations, both resistant and primary ALL cells from relapsed patients were sensitive to DOX-PMs-NPMBP. In detail, the half maximal inhibitory concentration (IC50) values of DOX-PMs-NPMBP were between 1.6- and 7.0-fold lower than those of DOX in cell lines and primary ALL cells, respectively; and apoptotic cells ratio was over 2-fold higher in DOX-PMs-NPMBP than DOX. Mechanistically, p53-driven apoptosis induction and cell cycle arrest played essential role in DOX-PMs-NPMBP-induced anti-leukemia effects. Moreover, DOX-PMs-NPMBP significantly inhibited tumor growth and prolonged mouse survival of ALL xenograft models; and no systemic toxicity occurrence was observed after treatment during follow-up. In conclusion, these data indicate that DOX-PMs-NPMBP may significantly exert growth inhibition and apoptosis induction, and markedly improve DOX antileukemia activity in resistant ALL cells. This novel drug delivery system may be valuable to develop as a new therapeutic strategy against multidrug resistant ALL.
- Abstract
- 1
- 10.1182/blood.v112.11.294.294
- Nov 16, 2008
- Blood
Aberrant Splicing of the SLP65 SH2 Domain Enables Pre-B Cell Transformation and Compromises the Leukemia-Suppressive Function of the Pre-B Cell Receptor
- Abstract
- 10.1182/blood.v120.21.2563.2563
- Nov 16, 2012
- Blood
Suppressor of Cytokine Signaling (SOCS) Molecules Are Critical to Balance Oncogenic Signaling Strength in Ph+ ALL.
- Abstract
- 10.1182/blood.v122.21.229.229
- Nov 15, 2013
- Blood
Inhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia
- Front Matter
- 47
- 10.1053/j.seminhematol.2008.09.011
- Dec 19, 2008
- Seminars in hematology
Acute Lymphoblastic Leukemia: Introduction
- Abstract
- 10.1182/blood.v116.21.274.274
- Nov 19, 2010
- Blood
Pre-B Cell Receptor Signaling Distinguishes E2A-PBX1 From Other Subtypes of Acute Lymphoblastic Leukemia
- Abstract
- 1
- 10.1182/blood.v110.11.4205.4205
- Nov 16, 2007
- Blood
Ex Vivo Activity of Bortezomib and Dexamethasone Combinations Against Childhood Acute Leukemia Cells.
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