Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia.

Haichang Li,Duoli Xie,Tieliu Shi,Chengping Wen,Lin Huang

doi:10.18632/oncotarget.16983

Abstract

Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients’ molecular features. Our method of formulating CMs based on patients’ stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization.

Highlights

Acute myeloid leukemia (AML) is one of the hematopoietic malignancies characterized by uncontrolled proliferation of myeloblast
The investigation indicated that 43 proteins encoded by differential expression gene (DEG) have explicit influence on AML including negative correlation with adverse prognosis (ATP1B1, HOXB4, MN1) [17,18,19] and promoting cell proliferation (DLL3) [20]
447 proteins have 7,494 interactive partners and the degree of them in the network was listed in descending order in Supplementary Table 3. 197 proteins respectively encoded by 111 down-regulated genes (OBSL1, myosin heavy chain (MYH9), ATXN1, etc.) and 86 up-regulated genes (BMI1, DBN1, CD81, etc.) possess greater than or equal to 25 interactions, covering 31 key proteins

Summary

Introduction

Acute myeloid leukemia (AML) is one of the hematopoietic malignancies characterized by uncontrolled proliferation of myeloblast. On contrary to advances in cytogenetic analysis at diagnosis and prognostic stratification, the pharmacology therapy researches of AML seem to be barely satisfactory which remain almost unchanged for nearly 40 years [1, 2]. Hematopoietic stem cell transplantation and chemotherapy are the main medical approaches for AML treatment, but the outcome is not ideal with the five year survival rate of AML patients appropriately low to 20% [3]. Only patients under 60 years old are suggested to take chemotherapy because of the incidental grievous damage to normal cells, leaving seldom treatment options for the rest patients [4]. The increasing number of identified SL gene pairs provides a promising in selective cytotoxicity to tumor cells and meantime reduces side effect of traditional chemotherapy [5]. Researchers working on AML treatments are seeking the www.impactjournals.com/oncotarget

Methods

Results

Conclusion