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

Blood. 2010 Jun 24;115(25):5214-21. doi: 10.1182/blood-2009-12-258822. Epub 2010 Apr 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Arginase / pharmacology*
  • Arginase / therapeutic use
  • Arginine / metabolism
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cyclin D3 / metabolism
  • Cytarabine / pharmacology
  • Disease-Free Survival
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation
  • Polyethylene Glycols*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Survival Rate
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • CCND3 protein, human
  • Cyclin D3
  • Cytarabine
  • Polyethylene Glycols
  • Arginine
  • Arginase