An analysis of the effect of myeloproliferative neoplasm-derived extracellular genomic materials on endothelial cells

Myeloproliferative Neoplasm(MPN) is basically a group of hematopoietic stem cell(HSC) caused disease affecting blood cell formation. This disease can affect different HSC lines and can be examined in different subgroups. JAK2V617F and BCR- ABL1 mutations are critical mutations for MPNs. These mutations were detected in MPN patient endothelial cells(EH) and were thought to play a role in thrombo-embolic events frequently seen in the disease. However, the exact mechanism of its occurrence is not yet known. Genometastasis is based on release of an oncogene from a cancer cell to circulation for transportation, transfection of a susceptible cell, and becoming malignant of the cell. This study aims to show that the detected mutation in EH occurs through genometastasis and causes some changes in EH after genometastasis. Firtsly, DNA from sera collected from biallelic JAK2V617F mutation carrier Human Erytroleukemia(HEL) cells and BCR-ABL1 carrier K562 cell line was isolated; mutation was detected in HUVECs. Mutant HUVECs were examined for apoptosis, proliferation, and surface proteins(CD106, CD141, CD146, CD309, CD54, CD31 ve CD142). Although there were no significant changes for apoptosis, proliferation and some surface proteins, the decrease and increase in CD141 and CD142 proteins compared to control, respectively, were statistically significant. Mutant HUVEC was cultivated and both mutations were detected again despite sub-culturing. As a result, extracellular genomic materials in the circulation can integrate into the genome of the endothelial cells and cause changes in the protein level of the cells. This study sheds light on the importance of genometastasis in carcinogenesis.