Establishment of an animal model for Waldenström's macroglobulinemia.
OBJECTIVE
Waldenström's macroglobulinemia (WM) is a low-grade lymphoplasmacytoid lymphoma characterized by production of monoclonal immunoglobulin M (IgM). The present study was undertaken with the aim of developing a novel nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of WM.


METHODS
Pairs of bone particles derived from adult humans were successfully implanted intramuscularly in NOD/SCID mice. Each mouse was implanted with a bone fragment taken from a neoplastic disease-free individual in the one hind limb and with a different biopsy taken from a WM patient in the other.


RESULTS
All mice implanted with the bone marrow core biopsies had increased levels of serum IgM 1 month following the implantation onward. Histopathologic and immunohistochemical analysis showed that in approximately half of the mice WM cells metastasized from the WM bone implant to the distantly implanted non-WM bone. Serum IgM value records of all mice correlated with histopathological observations and immunohistochemical analysis for neoplastic cell density and metastatic growth.


CONCLUSIONS
Results obtained in the present study suggest that IgM-producing WM cells not only retained viability in the bone marrow of the WM bone biopsy, but also metastasized to the normal bone marrow of the distant bone implant. The mouse model reported here improves on existing models of WM by recapitulating the adult human bone marrow microenvironment of abnormal WM neoplastic cells.
Tsingotjidou
Anastasia S
AS
Laboratory of Anatomy and Histology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Greece. astsing@vet.auth.gr
Emmanouilides
Christos E
CE
Siotou
Eleni
E
Poutahidis
Theofilos
T
Xagorari
Angeliki
A
Loukopoulos
Panayiotis
P
Sotiropoulos
Damianos
D
Bekiari
Chryssa
C
Doulberis
Michael
M
Givissis
Panagiotis
P
Fassas
Athanassios
A
Anagnostopoulos
Achilles
A
D000818:Animals; D002470:Cell Survival; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D009362:Neoplasm Metastasis; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology / Q000473:pathology
D007075:Immunoglobulin M