Maya Kartik

Stage-Focused Transcriptomic Profiling Reveals Distinct Gene Expression Patterns in Myeloproliferative Neoplasm Subtypes

Started Apr. 25, 2024

Abstract or project description

Previous gene expression profiling of Myeloproliferative Neoplasms (MPNs) have found a variety of abnormally regulated pathways and biological processes that contribute to these blood cancers. However, prior studies have generally focused on each MPN’s molecular profile on its own, without considering the patterns and differences in gene expression between MPNs to gain greater insights into each disease. To address this gap, transcriptomic analysis, through a comparative lens, of CD34+ BMMC and PBMC cells in patients with Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis and Secondary Myelofibrosis, and healthy controls was conducted. By using differential gene expression analysis, various types of visualization, and Gene Ontology Enrichment analysis, sets of genes and microRNA were identified whose expression patterns differentiated each MPN subtype. Specifically, Polycythemia Vera samples demonstrated dysregulation of a cohort of genes associated with microRNA, while Primary Myelofibrosis was distinguished by potential cytogenetic abnormalities, and Secondary Myelofibrosis by elevated inflammatory signatures. Additionally, components of the JAK/STAT pathway were identified to be consistently dysregulated across all the MPN subtypes under study, confirming their central role in MPN pathogenesis. These findings not only clarify upon our current understanding of the gene expression profile of these major MPN subtypes, but identify possible stage-specific biomarkers–such as upregulation of genes encoding cytokine receptors, and other facilitators of pro-inflammatory processes–to detect early stage MPN progression to Myelofibrosis. By uncovering biomarkers to predict disease transitions, this study lays the foundation for future MPN progression testing via the transcriptome to aid in the management of the disease and design more personalized treatment strategies.