EFFECTS OF PROLONGED TREATMENT WITH EPIGALLOCATECHIN-3-GALLATE IN AN ANIMAL MODEL OF MYELODYSPLASTIC SYNDROME"

• Grant number: 23/14472-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: January 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Murilo Jorge Lutfi
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/21801-2 - Predictors of severity and new treatments for bone marrow neoplasias, AP.TEM

Abstract

Myelodysplastic syndrome (MDS) is a bone marrow disease that affects the production of blood cells, with a risk of developing into acute myeloid leukemia. Treatment options are limited, highlighting the need for alternative therapies. Compounds derived from green tea, such as (-)-epigallocatechin-3-gallate (EGCG), have shown therapeutic potential in leukemia models. However, their effect on MDS is not fully understood. This project aims to investigate the causes of EGCG-induced splenic hematopoiesis in an animal model of MDS, observed in an ongoing study. The hypotheses to be tested would be whether the compound induces a reduction in CXCR4 expression in the bone marrow, by modulating HIF, resulting in extramedullary hematopoiesis, or whether it induces the constitutive activation of tyrosine kinase pathways and therefore the transformation of a myelodysplastic neoplasm into a myeloproliferative neoplasm. The methodology includes the analysis of material extracted from transgenic mice with MDS submitted or not to treatment with EGCG. Immunohistochemical analysis will be carried out on spleen and bone marrow to examine the expression of STAT3, pSTAT3, STAT5, pSTAT5 and CXCR4. Immunoblotting will also be carried out for JAK1, JAK2, STAT3 and STAT5 proteins in protein extracts from total bone marrow, spleen and liver.RNA sequencing (RNA-seq) will also be performed to investigate the transcriptome of treated animals and identify activated signaling pathways, including the JAK/STAT and CXCR4 pathways. In addition, a survival assessment will be carried out on a group of animals treated with EGCG to understand the impact of treatment on longevity.