Pegylated arginase I: a potential therapeutic approach in T-ALL Article

Full Text via DOI: 10.1182/blood-2009-12-258822 PMID: 20407034 Web of Science: 000279113100014

Cited authors

  • Hernandez, Claudia P.; Morrow, Kevin; Lopez-Barcons, Lluis A.; Zabaleta, Jovanny; Sierra, Rosa; Velasco, Cruz; Cole, John; Rodriguez, Paulo C.


  • Adult patients with acute lymphoblastic T cell leukemia (T-ALL) have a very poor prognosis and few effective therapeutic options. Therefore, novel therapies that increase the efficacy of the treatments and that prolong T-ALL patient survival are needed. Malignant T cells require high concentrations of nutrients to sustain their increased rate of proliferation. In this study, we determined whether L-Arginine depletion by the pegylated form of the L-Arginine-metabolizing enzyme arginase I (peg-Arg I) impairs the proliferation of malignant T cells. Our results show that peg-Arg I depleted L-Arginine levels in vitro and in vivo. In addition, treatment of malignant T-cell lines with peg-Arg I significantly impaired their proliferation, which correlated with a decreased progression into the cell cycle, followed by the induction of apoptosis. Furthermore, peg-Arg I impaired the expression of cyclin D3, a fundamental protein in T-ALL proliferation, through a global arrest in protein synthesis. Injection of peg-Arg I plus chemotherapy agent Cytarabine prolonged survival in mice bearing T-ALL tumors. This antitumoral effect correlated with an inhibition of T-ALL proliferation in vivo, a decreased expression of cyclin D3, and T-ALL apoptosis. The results suggest the potential benefit of L-Arginine depletion by peg-Arg I in the treatment of T-cell malignancies. (Blood. 2010;115(25):5214-5221)


Publication date

  • 2010

Published in

International Standard Serial Number (ISSN)

  • 0006-4971

Start page

  • 5214

End page

  • 5221


  • 115


  • 25