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Pleiotropic role of chemokines in Multiple Myeloma, study in the 5TMM model

dinsdag, 8 mei, 2012 - 16:00
Campus: Brussels Health Campus
Faculteit: Medicine and Pharmacy
auditorium P. Brouwer
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doctoraatsverdediging

This dissertation investigates the role of
chemokines in the development of Multiple
Myeloma (MM). Despite intensive research, multiple
myeloma remains an incurable plasma cell
malignancy, characterized by the accumulation of
the malignant cells in the bone marrow (BM) where
they modulate the microenvironment to their
needs, inducing osteolysis and angiogenesis. This
leads to pathological fractions, anemia and
hypercalcemia. Many questions still remain
regarding the development of the disease. A MM
cell most likely develops from a post switch B cell
and then enters the BM from the blood circulation
or at least spreads over the BM. Chemokines play
an important role in this process as they attract the
MM cells to the BM. Moreover, chemokines have
also been implicated in processes such as
osteolysis and angiogenesis.

In this work we investigated several chemokines
and their pleiotropic role in the development of MM
in the murine 5TMM model. 5TMM models initially
originated spontaneously in aging C57BL/KaLwRij
mice and have since been propagated in young
syngeneic mice by intravenous transfer of the
diseased BM. The models closely represent the
human disease.

We found that several molecules such as insulinlike
growth factor-1 (IGF-1), stromal cell derived
factor 1∝ (SDF1∝) and macrophage inflammatory
protein 1∝ (MIP1∝) are not only chemotactic
proteins for MM cells but also have pleiotropic
roles in the development of MM. Targeting these
chemokines in vivo proved to have therapeutic
value and could thus possibly contribute to the
development of novel drugs in the future.