Download Document

Ph.D. Student
Enrolment
Project Title
: Cand.med Ida Bruun Kristensen
: 1 September 2009
: "Osteoblast and osteoclast regulation in the pathophysiology of the bone disease
in multiple myeloma"
Supervisors
: Professor, dr.med. Niels Abildgaard
Senior Registrar, ph.d. Jacob Haaber Christensen, both Department of
Haematology, Odense University Hospital,Professor, dr.med Henrik Ditzel,
cand.scient, ph.d Maria Lyng Petersen, both Institute of Molecular Medicine,
Cancer and Inflammation group
Institute
: Institute of Clinical Research
Research Unit : Haematology
Abstract:
Aims: To reveal genes and cellular regulatory mechanisms of importance for development of
osteolytic bone disease (OBD) in multiple myeloma.
Background: Approximately 300 patients are each year in Denmark diagnosed with multiple
myeloma. Two thirds of these patients have OBD at the time of diagnosis while most of the rest
develops it during the course of the disease. OBD causes bone pain, hypercalciaemia and
pathological fractures. OBD is known to be caused by an overactivation of the osteoclasts without
compensatory osteoblast activation. The mechanisms of osteoblast inhibition are not clear.
Material and Methods: Snap-frozen bone biopsies, bone-marrow aspirates, serum and urine samples
are collected from all patients at the time-point of diagnostic work-up for multiple myeloma
(inclusion ongoing) together with clinical data. Also bone-marrow biopsies and aspirates are
collected from 20 healthy volunteers (inclusion ongoing). The material is added to a biobank with
amplificated cDNA from malignant plasma cells from >170 multiple myeloma patients. Focused
quantitative PCR (qPCR) analyses for ostelytic regulatory candidate genes (FRZB, HGF, SDC1,
cMET) have been performed. Bone marrow aspirates are used for flow sorting of malignant plasma
cells and mesenchymal steml cells (MSC). Gene expression profiling of MSC from patients with
different degrees of OBD, MGUS and healthy volunteers is planned. Osteoblast isolation with Laser
Capture Microdissection from slices of snap frozen bone marrow biopsies and gene expression
profiling with qPCR are planned.
Status: Patient inclusion ongoing (>30 included at present). Healthy volunteers have been recruited,
material collection ongoing. qPCR of plasma cells from myeloma patients showed an association
between expression of FRZB and degree of OBD (p<0.05), and an association between HGF and
cMET expression and OS (p<0.05). A sorting protocol for malignant plasma cells (CD45/CD38+/CD138+) and the rare MSC (CD34-/CD45-/CD73+/CD271+) is currently evaluated, and
amplification protocols of small amount of cDNA for gene expression profiling are being tested.
Keywords: Oncology and Haematology