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

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.

journal_name

Haematologica

journal_title

Haematologica

authors

Chamuleau ME,van de Loosdrecht AA,Hess CJ,Janssen JJ,Zevenbergen A,Delwel R,Valk PJ,Löwenberg B,Ossenkoppele GJ

doi

10.3324/haematol.13113

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

1894-8

issue

12

eissn

0390-6078

issn

1592-8721

pii

93/12/1894

journal_volume

93

pub_type

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