Evaluation of the Effects of Artesunate in an Animal Model of Myelodysplastic Syndrome by RNA Sequencing

• Grant number: 24/15769-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Eduardo Rodrigues Gonçalves
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Traditional Chinese Medicine (TCM) has been garnering increasing interest from conventional science. Artemisia annua, a key component of TCM, contains artemisinin, which has significant therapeutic applications, especially in the treatment of malaria. Artesunate, derived from artemisinin, has been studied for its diverse therapeutic properties, including anti-inflammatory, antidiabetic, and antitumor activities. Previous studies published by our group suggest that artesunate has therapeutic potential for Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), a malignant hematological disease with high mortality. The overall objective of this study is to identify and characterize the genetic modifications induced by artesunate in an animal model of MDS using RNA sequencing (RNA-seq) data analysis. The specific objectives include highlighting biological pathways modulated by artesunate, evaluating the effects of treatment on gene transcription in MDS models, and establishing correlations with previous studies. To achieve this, transgenic mice presenting the NUP98-HOXD13 gene fusion, which develop MDS, will be treated with artesunate for four months, with a comparative analysis between treated and control groups. After treatment, spleen and bone marrow samples will be collected and processed for RNA extraction. RNA-seq will be performed to analyze gene expression profiles, using bioinformatics tools for data quantification, normalization, and functional analysis. The construction of genetic interaction networks will be conducted to elucidate the underlying mechanisms of artesunate's effects. This study is expected to provide insights into the effects of artesunate in MDS models, identifying modulated biological pathways and correlating these findings with previous results. This study may contribute to the development of new therapeutic approaches for MDS and AML, enhancing the understanding of the mechanisms involved in the response to artesunate treatment.