Indoleamine 2, 3-dioxygenase expression in cells of human acute monocyte leukemia (M(5)) and acute lymphocyte leukemia and therapeutic effect of its inhibitor 1-methyl tryptophan.
The objective of this study was to investigate the expression and function of indoleamine 2, 3-dioxygenase (IDO) in leukemia. The IDO expressions in human acute monocyte leukemia (M(5)) and acute lymphocyte leukemia (ALL) were detected by immunofluorescence staining. Constructed leukemia mouse model was used to observe whether the IDO inhibitor, 1-methyl tryptophan (1-MT), has any effect in treating leukemia. The experimental group were fed with 1-MT solution every day while the mice in control group had no further treatment. The results showed that the average ratios of IDO expression were 29.4 +/- 11.2% in M(5) patients and 24.7 +/- 7.96% in ALL patients respectively. After statistical test, IDO expression level in leukemia cells was significantly higher than that of normal mononuclear cells. The tumor decreased gradually in mice treated with 1-MT. At the terminal point of the experiment (88 days after vaccination), the average survival time in the experimental group was 42.3 days while the mice in control group only lived 15.1 days in average, which difference was statistically significant (P < 0.05). Some of the leukemia mice in the experimental group long-term survived without tumor (more than three months after vaccination). It is concluded that human acute monocyte leukemia (M(5)) and acute lymphocyte leukemia (ALL) express IDO, and both can be treated by 1-MT in mice.
Sun
Jing-Xin
JX
Department of Hematology, The Second Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
Zhang
Wang-Gang
WG
Chen
Yin-Xia
YX
Zhao
Wan-Hong
WH
Tian
Wei
W
Yang
Yun
Y
Liu
Su-Hu
SH
D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007939:Leukemia L1210 / Q000188:drug therapy; D015456:Leukemia, Biphenotypic, Acute / Q000188:drug therapy / Q000201:enzymology*; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008875:Middle Aged; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan; C525396:1-methyltryptophan