Expression of indoleamine 2,3-dioxygenase in leukemic cells indicates an unfavorable prognosis in acute myeloid leukemia patients with intermediate-risk cytogenetics

Abstract

The immunomodulatory effects of indoleamine 2,3-dioxygenase (IDO) are ascribed to its ability to catalyze breakdown of the essential amino acid l-tryptophan. We applied reverse transcription-polymerase chain reaction (RT-PCR) to examine IDO mRNA expression in acute myeloid leukemia (AML) blasts, and investigated its clinical significance. We enrolled 62 patients with AML between April 2005 and March 2013. Bone marrow-derived mononuclear fractions were separated and extracted mRNA was amplified by PCR. RT-PCR showed that the bone marrow of 23 patients expressed IDO mRNA but not in 39. IDO mRNA expression did not significantly differ among cytogenetic risk profiles. The 3-year overall survival rates for patients with and without IDO mRNA expression were 39% and 74%, respectively (p < 0.005). The rates for patients with intermediate-risk cytogenetics with and without IDO mRNA expression were 16% and 70%, respectively (p < 0.005). The expression of IDO mRNA was associated with a poor prognosis of AML.

Keywords::

• Immunological tolerance
• prognostic factor
• l-tryptophan catabolism
• acute myeloid leukemia
• indoleamine 2,3-dioxygenase

Acknowledgments

This study proceeded in cooperation with the Gifu Hematology Study Group. We thank the participating physicians for providing bone marrow samples from the patients: Drs. Takeshi Takahashi, Michio Sawada, Toshiki Yamada, Takeshi Yoshikawa, Hideko Goto, Naoe Goto, Senji Kasahara, Nobuhiro Kanemura, Hiroshi Nakamura, Takuro Matsumoto and Eri Takada. We also thank Mss. Chiyoko Sano, Hitomi Fujisawa, Shōko Sumi and Eriko Kunishima for secretarial and technical assistance.

Potential conflict of interest:

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