Haematologica 2003 - Supplements

11. Derenne S, Amiot M, Barille S, Collette M,
Robillard N, Berthaud P, Harousseau JL, Bataille R. Zoledronate
is a potent inhibitor of myeloma cell growth and secretion of IL-6
and MMP-1 by the tumoral environment. J Bone Miner Res.
1999;14:2048-2056.
12. Berenson JR, Hillner BE, Kyle RA, Anderson K,
Lipton A, Yee GC, Biermann JS. American Society of Clinical
Oncology clinical practice guidelines: the role of bisphosphonates
in multiple myeloma. J Clin Oncol. 2002;20:3719-3736.
Waldenström's macroglobulinemia:
update from the 2nd International
Workshop on Waldenström's
macroglobulinemia
GENETIC BASIS AND PATHOGENESIS OF
WALDENSTRÖM’S MACROGLOBULINEMIA
LM Pilarski, SS Sahota, R Fonseca, H Avet-Loiseau, N
Mitsaides, ML McMaster, D Leitch, RG Owen, S Adamia &
J Shaughnessy
The Second International Workshop on Waldenström’s
Macroglobulinemia (WM) held in September 2002 brought
together emerging data on the biology and genetic characteristics
of WM, and these findings are summarized and updated here.
WM, a slowly progressive clonal lymphoid disorder, involves a
lymphoplasmacytic BM proliferation accompanied by a serum
monoclonal IgM component, various autoimmune disorders, and
organomegaly in some patients. Although WM includes both
lymphocytic and plasmacytoid cells, a clonal relationship
between the B cell subpopulations in WM is likely and direct
evidence is now emerging to address this issue. The dynamic
differentiation of the WM clone over time and in the face of
treatment clearly has potentially profound implications for
clinical management of the disease. In effect, the clinical
therapeutic arsenal must hit a “moving target”. Although
phenotypic characterization of WM suggests that the malignant
cells express sIgM/CD19/CD20, the plasmacytic components
expressing CD38/CD138 can vary. Interestingly, phenotypic
markers normally associated with T-cells also appear to be
expressed by some clonal cells. The analysis of Ig variable region
(V) genes in WM has established a monoclonal tumor identity,
and indicates origins from a cell which has undergone somatic
mutation and transforms prior to isotype switch. This presentation
will discuss new findings relating to the cell types that comprise
WM, the clonal origins, cytogenetics and familial relationships in
WM. It will also address novel gene profiling and proteomic
analysis of WM, comparative analysis of IgH switch region
translocations and the relationships between IgM myeloma and
WM, dysregulation of apoptosis and potentially oncogenic
overexpression of hyaluronan synthases in WM. The
identification of molecular WM signatures will enable the extent
of minimal disease to be readily monitored and early relapse
detected. In addition, with the impending availability of sensitive
molecular tests to detect the WM signature, the potential exists to
identify novel therapies that may be better able to eradicate WM
clonal populations.
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