Functional and genomic responses of hematopoietic and cancer stem cells in hypoxic conditions

Purpose: Myeloproliferative neoplasia is a disease with increased proliferation of myeloid blood cells, caused by somatic mutations. In this study, it is aimed to show whether myeloproliferative disorders leads to a change in HIF1α and NOS3 gene expression caused by hypoxic conditions of bone marrow microenvironment. Materials-Methods: Bone marrow microenvironment was applied to healthy controls and healthy patients' the subgroups of Hematopoietic Stem Cells (HSC), CD34+ and CD34- with different oxygen pressure values (0%, 1%, 5%) using the CellAsic ONIX device. cDNA synthesis and RNA isolation were performed after 24 hours of cell culture. Quantitative Real-Time PCR techniques were used to investigate the changes in gene expression. Findings: Higher concentration of RNA samples were isolated from CD34+ subgroups from MPN patients compared to CD34- groups. HIF1α and NOS3 gene expressions increased in pateints' stem cells than controls'. The differences between the heterozygous and wild-type allele for JAK2V617F exchange were not significant. In not classified MPN patients with JAK2V617F heterozygous allele, expression of NOS3 under hypoxic conditions was found to be decreased compared to control. Results: The bone marrow microenvironment or stem cell niche is a complex system that supports the function of hematopoietic stem and progenitor cells. According to the study, it was seen that the response to hypoxia and anoxia of CaSC should be evaluated according to the type of cancer. The MPN genotype and response to hypoxia should be evaluated according to the disease. It is clear that more comprehensive studies in this subject are needed.