Browsing by Author "Rantanen, Frida"

Essential thrombocythemia (ET) is a clonal hematopoietic disease characterized by an abnormal increase of platelets in the circulation, with increased risk of thrombosis and hemorrhage. Despite megakaryocytes having a central role in the disease, few studies have investigated their gene expression in ET. The aim of this study is to characterize the gene expression profiles of megakaryocytes from ET patients harboring different driver mutations, and increase the knowledge of the molecular mechanisms underlying the pathophysiology of the disease. In this study, samples were obtained from healthy donors and ET patients with JAK2 V617F, CALR Type I, CALR Type II driver mutations and triple-negative patients. Following megakaryocyte culture from peripheral blood and RNA sequencing, the data was pre-processed and analyzed using differential gene expression analysis. The downstream analysis was conducted using pathway enrichment analysis tools. The analysis revealed that all mutants shared common deregulated genes related to processes involving platelets and coagulation. However, it was shown that CALR and JAK2 V617F mutants also have distinct patterns of gene expression. CALR Type I mutants had a unique gene expression signature consisting of genes related to immune response, as well as metabolic, regulatory, proliferative, and inflammatory pathways, while CALR Type II mutants had unique genes related to ribosomes. The CALR mutants also shared a common anti-inflammatory response signature which set them apart from JAK2 V617F mutants. In conclusion, this study shows that the gene expression profiles of ET mutants are heterogeneous. Moreover, the results provide new insights into the gene expression profiles of CALR mutants that distinguish them from the other mutants. Further experiments using single-cell RNA sequencing methods could build upon these findings and uncover the observed gene expression discrepancies between CALR and JAK2 mutants with increased accuracy.