Human recombinant arginase I(Co)-PEG5000 [HuArgI(Co)-PEG5000]-induced arginine depletion is selectively cytotoxic to human acute myeloid leukemia cells

Rita Tanios, Amira Bekdash, Elias Kassab, Everett Stone, Georges Georgiou, Arthur E. Frankel, Ralph J. Abi-Habib

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

In this study, we target arginine auxotrophy of AML cell lines using human arginase I cobalt-PEG5000. HuArgI(Co)-PEG5000 was cytotoxic to all AML cell lines tested. Mononuclear cells and CD34+ blasts were not sensitive demonstrating the selectivity of HuArgI(Co)-PEG5000-induced arginine deprivation. Addition of l-citrulline led to the rescue of five cell lines. The four cell lines that were not rescued by l-citrulline did not express argininosuccinate synthetase-1, indicating complete arginine auxotrophy. Inhibition of autophagy increased cell sensitivity to HuArgI(Co)-PEG5000 demonstrating the protective role of autophagy following arginine deprivation. We have shown that AML can be selectively targeted using HuArgI(Co)-PEG5000-induced arginine depletion.

Original languageEnglish (US)
Pages (from-to)1565-1571
Number of pages7
JournalLeukemia Research
Volume37
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • AML
  • Arginine
  • Autophagy
  • HuArgI(Co)-PEG5000

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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