Crosstalk between mutation landscape, immune dysregulation and microbiome - role in pathogenesis and progression of myeloproliferative neoplasms

Overview

Project Summary

Myeloproliferative neoplasms (MPNs) Philadelphia-negative  include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. These disorders are characterized by clonal hematopoietic stem cell proliferation, often driven by mutations in genes that codify tyrosine kinases as JAK2, CALR, and MPL. MPNs can lead to  complications such as thrombotic events or progress to leukemic transformation. Leukemic evolution is associated with acquired mutations in TP53, ASXL1, RUNX1, EZH2, and IDH1/2 genes. Additionally, inflammation and immune dysfunction play crucial roles in MPN initiation and progression. Inflammatory pathways are activated in hematopoietic stem cells, leading to the release of various cytokines. Oxidative stress and alterations in immune cells, including reduced natural killer and T cells, contribute to the disease. Moreover, the microbiome's role in modulating inflammation and myelopoiesis is increasingly recognized. 

Main Goals

The objectives of this project is to understand the interplay between mutation landscape, immune dysregulation, and the microbiome in order to further comprehending MPN pathogenesis, to identify prognostic factors, and to develop potential therapeutic targets.

Project Details