Haematologica
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Published online 2 September 2008
(Haematologica 2008, 10.3324/haematol.13112)
Copyright © 2008 by Ferrata Storti Foundation
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Original Article

High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome

Martine E.D. Chamuleau1, Arjan A. van de Loosdrecht1, Corine J. Hess1, Jeroen J.W.M. Janssen1, Adri Zevenbergen1, Ruud Delwel2, Peter J.M. Valk2, Bob Löwenberg2, Gert J. Ossenkoppele1

1 Department of Hematology, VU University Medical Centre, Amsterdam, the Netherlands;
2 Department of Hematology, Erasmus University Medical Centre, Rotterdam, the Netherlands

Correspondence: Martine E.D. Chamuleau, MD, Department of Hematology, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E-mail:m.chamuleau{at}vumc.nl

ABSTRACT

Indoleamine 2,3-dioxygenase degrades the amino acid tryptophan which is essential for T cells. Tryptophan depletion causes T-cell cycle arrest and solid tumors that express high levels of indoleamine 2,3-dioxygenase can create immune suppression. Recently, blasts of patients with acute myeloid leukemia were shown to express indoleamine 2,3-dioxygenase. We determined INDO (encoding gene for indoleamine 2,3-dioxygenase) mRNA expression in leukemic blasts of 286 patients with acute myeloid leukemia by gene-expression profiling. Results were validated by quantitative polymerase chain reaction analysis in blasts of an independent cohort of 71 patients. High INDO expression was correlated to significantly shortened overall and relapse-free survival. Correlation of INDO expression to relevant known prognostic factors and survival identified high INDO expression as a strong negative independent predicting variable for overall and relapse-free survival. Inhibition of indoleamine 2,3-dioxygenase expressed by myeloid leukemic blasts may result in breaking immune tolerance and offers new therapeutic options for patients with acute myeloid leukemia.

Key words: indoleamine 2, 3-dioxygenase, INDO, acute myeloid leukemia, immunesurveillance, immunetherapy.






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Copyright © 2008 by the Ferrata Storti Foundation.