High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome.
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.
Chamuleau
Martine E D
ME
Department of Hematology, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. m.chamuleau@vumc.nl
van de Loosdrecht
Arjan A
AA
Hess
Corine J
CJ
Janssen
Jeroen J W M
JJ
Zevenbergen
Adri
A
Delwel
Ruud
R
Valk
Peter J M
PJ
Löwenberg
Bob
B
Ossenkoppele
Gert J
GJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D055815:Young Adult
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D012334:RNA, Neoplasm