Oncotarget

Research Papers:

Pharmacometabolomics identifies dodecanamide and leukotriene B4 dimethylamide as a predictor of chemosensitivity for patients with acute myeloid leukemia treated with cytarabine and anthracycline

Guangguo Tan, Bingbing Zhao, Yanqing Li, Xi Liu, Zhilan Zou, Jun Wan, Ye Yao, Hong Xiong and Yanyu Wang _

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Oncotarget. 2017; 8:88697-88707. https://doi.org/10.18632/oncotarget.20733

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Abstract

Guangguo Tan1,*, Bingbing Zhao2,*, Yanqing Li2, Xi Liu2, Zhilan Zou2, Jun Wan2, Ye Yao2, Hong Xiong2 and Yanyu Wang2

1School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China

2Department of Hematology, The Central Hospital of Xuhui District, Shanghai, 20031, China

*These authors have contributed equally to this work

Correspondence to:

Yanyu Wang, email: yywang2017@126.com

Hong Xiong, email: hxiong@scrc.ac.cn

Keywords: pharmacometabolomics, metabolomics, acute myeloid leukemia, chemosensitivity, liquid chromatography-mass spectrometry

Received: July 05, 2017     Accepted: August 04, 2017     Published: September 08, 2017

ABSTRACT

Clinical responses to standard cytarabine plus anthracycline regimen in acute myeloid leukemia (AML) are heterogeneous and there is an unmet need for biological predictors of response to this regimen. Here, we applied a pharmacometabolomics approach to identify potential biomarkers associated with response to this regimen in AML patients. Based on clinical response the enrolled 82 patients were subdivided into two groups: complete remission(CR) responders (n=42) and non-responders (n=40). Metabolic profiles of pre-treatment serum from patients were analyzed by ultra-high performance liquid chromatography coupled with mass spectrometry and the metabolic differences between the two groups were investigated by multivariate statistical analysis. A metabolite panel containing dodecanamide and leukotriene B4 dimethylamide (LTB4-DMA) had the power capacity to differentiate the two groups of patients, yielding an area under the receiver operating characteristic of 0.945 (85.2% sensitivity and 88.9% specificity) in the training set and 0.944(84.6% sensitivity and 80.0% specificity) in the test set. The patients with high levels of LTB4-DMA and low amounts of dodecanamide had good sensitivity to chemotherapeutic agents. The possible reasons were that dodecanamide was produced by leukemic cells as a lipolytic factor to fuel their growth with a potential role in drug resistance and LTB4-DMA was a potent leukotriene B4 antagonist that could be applicable in the treatment of AML. These preliminary results demonstrates the feasibility of relating chemotherapy responses with pre-treatment metabolic profiles of AML patients, and pharmacometabolomics may be a useful tool to select patients that are more likely to benefit from cytarabine plus anthracycline chemotherapy.


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