Malignant hematopoietic stem cells and bone marrow stroma cells in myeloproliferative neoplasms - towards the development of novel therapies targeting the stem cells and their niche

Project: Dissertation

Research areas and keywords

UKÄ subject classification

  • Hematology


Philadelphia-negative myeloproliferative neoplasms (MPNs) are caused by JAK-STAT pathway-activating somatic mutations in hematopoietic stem cells (HSC). MPNs display diverse disease phenotypes, but it is not clear whether this is a result of HSC heterogeneity or other factors. Furthermore, current JAK inhibitor therapy is not curative, likely because MPN stem cells are not sufficiently targeted due to cell intrinsic properties and/or microenvironmental factors. In addition, cumulating evidence indicates that alterations of the hematopoietic microenvironment (HME) and the HSC niche are of critical importance for the development and progression of MPNs, but the exact mechanisms have not been identified yet.
The study of the malignant HSC and possible HME abnormalities is therefore key to gain insight into MPN disease pathophysiology and - in the long term - to develop more effective treatment strategies. We have established the tools to approach the identification and characterization of malignant MPN-HSCs, we have recently identified the phenotype of primary bone marrow stromal cells (BMSC) that can be applied to diseased bone marrow, and we have developed a stroma xenotransplantation model that allows to study the crosstalk of MPN stem cells with their niche.
Effective start/end date2018/05/01 → …