CCBIO Seminar: Lorena Arranz
Title: "Neuroglial dysregulation of the haematopoietic stem cell niche in myeloid leukaemias"
CCBIO seminar (BMED380) Thursday, April 30, 14.30, at the BBB, Auditorium 4
Apart from the interesting talks, the CCBIO seminars are a good way to meet CCBIO members and associates. Please feel free to circulate this invitation as all are welcome both to the lecture and the pizza get-together afterwards, during which the University Library will have a stand to inform you about open access, BORA and how you can get your author fees covered by the UiB.
Invited speaker: Lorena Arranz
Stem Cell Aging and Cancer Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø
Acute myeloid leukaemia (AML) is the most common form of acute leukaemia occurring in adults, its incidence increases with age and the prognosis for the older patient remains bleak. Overcoming these problems will require improved understanding of AML. Oncogenes frequently mutated in human AML that confer a survival advantage to the haematopoietic stem cell (HSC), such as RAS and FLT3, are only able to induce myeloproliferative neoplasms (MPN) in mouse models. This indicates that these lesions are insufficient to cause AML and suggests participation of other factors. Until recently the focus has been on the search for additional genetic mutations with little consideration of the bone marrow (BM) HSC niche. The latter has a significant influence on haemopoiesis under healthy conditions.
Further, our recent work uncovered an unprecedented role for the BM HSC niche in MPN pathological conditions. We specifically showed the role in disease progression of the neuroglial components and mesenchymal stem cells (MSC) in the BM with the JAK2-V617F mutation, which improves HSC survival. As an early event in the course of polycythemia vera, the mutant JAK2-V617F+ HSC promotes inflammation through IL-1β production. This leads to damage of BM sympathetic fibres and covering Schwann cells, causing MSC apoptosis. Loss of the inhibitory regulation exerted by these BM niche components then allows uncontrolled expansion of mutant JAK2-V617F+ HSC and worsens the inflammatory environment. The pathogenic role of these changes was demonstrated by prevention of further MSC apoptosis and inflammation through enhancement of adrenergic activity using a β3-adrenergic agonist. This treatment blocked disease progression in mice and will soon be confirmed in patients with MPN.
Currently, the primary aims of the recently established research group are to test the potential role of the BM niche in leukaemic transformation and to study the importance of this to human AML. Our recent research will be presented, followed by a glimpse over the research group, our ongoing research and future directions.
Chairperson: Bjørn Tore Gjertsen <firstname.lastname@example.org>, CCBIO
NB! After the seminar, CCBIO is pleased to invite you to a pizza get-together outside the auditorium. Everybody is welcome!