Erman L, Baruchel A, Goekbuget N, Schrappe M, Pui CH. L-asparaginase
Erman L, Baruchel A, Goekbuget N, Schrappe M, Pui CH. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer. 2011; 117: 23849. eight. Verma N, Kumar K, Kaur G, Anand S. L-asparaginase: a promising chemotherapeutic agent. Crit Rev Biotechnol. 2007; 27:452. 9. Stams WA, den Boer ML, Holleman A, Appel IM, Beverloo HB, van Wering ER, Janka-Schaub GE, Evans WE, Pieters R. Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia. Blood. 2005; 105:4223225. ten. Covini D, Tardito S, Bussolati O, Chiarelli LR, Pasquetto MV, Digilio R, Valentini G, Scotti C. Expanding targets to get a metabolic therapy of cancer: L-asparaginase. Current Pat AntiAurora A Biological Activity Cancer Drug Discov. 2012; 7:43. 11. Iwamoto S, Mihara K, Downing JR, Pui CH, Campana D. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. J Clin Invest. 2007; 117:1049057. 12. Douer D, Aldoss I, Lunning MA, Burke PW, Ramezani L, Mark L, Vrona J, Park JH, Tallman MS, Avramis VI, Pullarkat V, Mohrbacher AM. Pharmacokinetics-based integration of many doses of intravenous pegaspargase inside a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014; 32:90511. 13. Kobrinsky NL, Sposto R, Shah NR, Anderson JR, DeLaat C, Morse M, Warkentin P, Gilchrist GS, Cohen MD, 3871 OncotargetConfocal microscopyK562 and KU812 cells were seeded into 6-well plates at a density of 1 105mL and after that treated with 0.five IUmL of asparaginase. Soon after 24 h of incubation, cells were stained with Cyto-IDGreen dye and Hoechst 33342 at 37 for 30 min in accordance with the manufacturer’s protocol. Then the cells had been washed and re-suspended with PBS. A drop on the cell suspension had been taken to a glass microscope slide and overlaid using a coverslip and quickly analyzed by confocal microscopy. Positive controls have been treated with all the autophagy inducer Rapamycin at 50 nM for 12 h, and disposed with identical methods. Each of the procedures had been performed in the dark spot.Statistical analysisData from this study have been presented as mean values with standard deviations (SD). The statistical significance with the differences in between groups was evaluated by Student t test. , , and indicated P 0.05, P 0.01 and P 0.001, respectively.ACKNOWLEDGMENTSThis study was supported by National Crucial Fundamental Analysis Plan of China (2013CB932502, 2015CB931800) and Shanghai Science and Technology Funds (14431900200, 13431900303, 11431920104).
Chronic myeloid leukemia (CML) is usually a hematopoietic stem cell illness integrated within the broader diagnostic category of myeloproliferative neoplasms [1] that may be characterized by neoplastic overproduction of mostly granulocytes. CML is consistently connected with fusion by chromosome translocation of the breakpoint cluster region gene (BCR) at chromosome 22q11 to the Abelson gene (ABL1) at chromosome 9q34. This fusion gene BCRABL1 encodes for an oncoprotein (P210, a lot more seldom P190 or P230) using a ALK1 site strong constitutive activated tyrosine kinase activity inducing a number of downstream signals causing the transformation of hemopoietic stem cells [2]. The translocation t(9;22) could be detected by routine karyotype as Philadelphia (Ph) chromosome, though in 20 in the cases, the fusion gene arises from a variant translocation [3]. Two variant subgroups happen to be recognized: the uncomplicated variant group with the 22q segment translocated onch.