Haematologica 2003 - Supplements

221
Prolonged survival in the 5T2MM murine myeloma
model is associated with high proportions of CD45+
myeloma cells
Asosingh K, Willems A, Van Riet I, Van Camp B and
Vanderkerken K.
Department of Hematology & Immunology.Vrije Universiteit Brussel
Although both CD45+ and CD45- multiple myeloma (MM) cells
are observed in the bone marrow (BM) of MM patients, their
roles in myeloma biology are not completely understood. In our
previous works (Asosingh et al, Exp Hematol. 2000; Asosingh et
al, Clin Exp Metastasis, 2002) in the 5TMM murine model, we
were able to demonstrate that CD45+ 5T2MM cells are the
predominant in vivo BM homing population. This was
attribuatable to their high migration and invasion capacities. In
contrast to the CD45+ 5T2MM cells, the CD45- 5T2MM cells
have a high in vivo proliferative capacity. In a more recent report
(Asosingh et al, Blood, 2003) we demonstrated that 5T2MM
disease progression is an ongoing differentiation process of
CD45+ MM cells into CD45- MM cells. In the current work we
provide in vivo data indicating that CD45 subsets in the 5T2MM
model have an impact on the outcome of the disease. 92% of the
naïve mice injected with 5T2MM cells develop myeloma in 10-
12 weeks (terminally diseased) and hind leg paralysis. In these
animals the end stage 5T2MM cells are predominant CD45- (23.1
+ 11.1% CD45+ MM cells, mean + SD values) in analogy to the
common human situation. The remaining 8% of the animals have
delayed tumor progression (terminally diseased after 14-24
weeks, p< 0.002) with a complete different feature in the end
stage of the disease. In addition to the prolonged surival, these
animals had typically a bowed back and never got paralyzed. The
MM cells in the BM of these mice were predominant CD45+
(86.1 + 5.8%, mean + SD values, p