Malignant transformation of hematopoietic stem cells: pathophysiology and development of therapy
01 / 1988 - unknown
METIS Erasmus Universiteit Rotterdam
In this project we investigate abnormalities in the cellular responsiveness to hematopoietic growth factors, the expression, structure and function of hematopoie-tic growth factor receptors as well as alterations of signal transduction and transcripti-on that may contribute to the develop-ment of hematological malignancies. The abnormalities may influence the survival, cell cycle regulation, commitment or maturation of hematopoietic progenitor cells. The investiga-ti-ons on the genetic abnormalities of hemato-oncologic diseases extend towards the development of a specific diagnosis and the detection of minimal residual disease, as well as new therapeutic interventions of hematological malignancies. With respect to the development of new treatment strategies aimed at eradicating malignant hematopoietic progenitor cells, we address questions related to their sensitivity to chemotherapy and modulati-on of resistan-ce, the response to novel drugs that target specific genes, experimental approaches of stem cell transplantation and the genetic modificati-on of hematopoietic stem cells. The modalities are explored in relevant animal models as well as in clinical studies.