Scientific Presentations Summer 2009 - Dana-Farber/Harvard ...

Validation of an anti-Dkk1 monoclonal antibody for
the treatment of bone disease in multiple myeloma
Cienna Wesley
Mentor: Noopur Raje, MD
Scientific Advisors: Samantha Pozzi, MD and Sonia Vallet, MD
Massachusetts General Hospital
Multiple Myeloma (MM) is a cancer of the bone marrow caused by a proliferation of
malignant plasma cells. MM plasma cells interfere with bone remodeling, acting on
osteoblasts (OB) (bone producing cells) and the osteoclasts (OC) (bone resorption
cells) creating an imbalance in their number and function resulting in the development
of osteolytic lesions, typical of the disease. Increased serum concentration of
Dkk1, an inhibitor of the Wnt pathway essential for osteoblastogenesis, has been
observed in MM patients. It correlates with osteolytic lesions and inhibits the activity
of OB in MM patients. It is our hypothesis that targeting this serum protein will
enable us to restore bone homeostasis in MM and thus prevent bone disease. We will
test this hypothesis by using a novel anti-Dkk1 monoclonal antibody with the goal
of decreasing bone disease in MM.
We have previously identified its effects on OB. Here I will focus on effects of anti-
DKK1 on OC. OC were generated from bone marrow mononuclear cells derived
from MM patients. After 2-3 weeks of culture, cells were fixed and stained for Tartrate
Resistant Acid Phosphatase (TRAP) characteristic of OC and counted. Our
data demonstrates a reduction of OC number in the treated samples compared with
control. We will next test whether OC function is impacted as well. These experiments
will highlight the effects of anti-DKK1 on the OC in MM.