Haematologica 2003 - Supplements

UPN
MM
type
Stage
Prev.
Treatment
CCR7
%
CCR7
MIF
CXCR4
%
CXCR4
MIF
CXCR5
%
CXCR5
MIF
1 IgG IIA 1 1 2 96 123 23 29
2 IgG IIIB 1,2 11 9 100 95 32 8
3 BJ IIA 1 18 11 100 236 87 32
4 IgG IIA 1 14 8 100 223 71 46
5 IgA IIIA 1,2 4 3 100 85 11 14
6 IgA IIIA 1 4 2 97 98 13 20
7 IgG IIA 1,2 8 3 97 53 26 12
8 IgA IA 4 4 1 97 51 - -
9 IgA IIIB 1,3 2 3 89 60 - -
10 BJ IIIB 1,2,3 8 2 98 124 - -
11 IgG IA 4 3 6 70 34 16 18
12 IgG IA 4 3 4 99 88 48 39
Med 6.66 4.50 95.50 105.83 37.57 23
SD 5.28 3.23 8.61 64.16 29.57 13.42
1:QT , 2-PBSCT, 3- Thalidomide, 4- Non treated
Correlation of chemokine receptor levels and clinical status after
treatment will be presented
Conclusions. The expression of CXCR4, CXCR5 and CCR7 were
demonstrated in bone marrow samples of patients with multiple
myeloma. The differents levels of expression could be related to
the heterogenous MM clinical patterns and to previous treatment.
More studies are needed to evaluate the exact significant of these
expression and to dilucidate this possible correlation with clinical
MM status and with novel therapies that could influence
plasmocyte adhesion mechanism as thalidomide.
References:
1.-Moller C et al. Expresión and function of chemokine receptors
in múltiple myeloma. Leukemia 2003, 1:203-210
2.-Hargreaves DC et al. A coordinated change in chemokine
responsiviness guides plasma cell movements. J.Exp.Med. 2001;
194:1, 45-56
3.-Wherli N et al: Changing responsiveness to chemokines allows
medullary plasmablasts to leave lymph nodes. Eur. J. Immunonol.
2001, 31:609-616
057
pHENOTYPIC AND FUNCTIONAL CHARACTERIZATION
OF CHEMOKINE RECEPTORS ON MALIGNANT plasma
cells IN PATIENTS WITH MULTIPLE MYELOMA
L. Trentin, M. Facco, M. Miorin, A. Cabrelle, I. Baesso, M.
Bortoli, D. Carollo, G. Binotto, L. Nicolardi, C. Agostini, F.
Adami, R. Zambello, G. Semenzato.
Dept. Clinical & Experimental Medicine, Clinical Immunology
Branch, Padua University School of Medicine, 35128 Padova, Italy.
Chemokine receptors and their ligands play a relevant role in the
organogenesis of lymphoid tissues and in the trafficking of B
lymphocytes. Several data reported in the literature indicate the
involvement of chemokines and their receptors in the
pathogenesis of lymphoid neoplasias of B-cell lineage have been
reported in the literature, whilst few data are available on plasma
cells obtained from patients with multiple myeloma.
In this study freshly isolated malignant plasma cells obtained
from the bone marrow of 30 patients with multiple myeloma, 3
myeloma cell lines and 5 normal PC suspensions were
investigated by flow cytometry for the expression of chemokine
receptors, including CCR1, CCR2, CCR3, CCR5, CCR6,
CXCR1, CXCR2, CXCR3, CXCR4, CXCR5. In some patients
the analyses were also performed on malignant plasma cells
recovered from peripheral blood and pleural effusions.
Flow cytometry analysis showed that all the samples studied were
CD38+. This antigen was expressed at high density on myeloma
PC. CD138 was expressed in all the patients studied; CD117 was
significantly expressed in 1/3 of our patients with MM; CD56,
instead, was expressed on about half of patients. Concerning
chemokine receptors, we showed that CXCR4 is regularly
expressed on PC obtained from MM patients and MM cell lines.
Other receptors, i.e. CCR1, CCR5, CXCR1, CXCR2, CXCR3
and CXCR5 are commonly absent on myeloma cells obtained
from patients. CCR1 and CXCR3 are found to be expressed in
RPMI-8226 and OPM-2 cell lines. Functional in vitro evaluation
showed a consistent migration of malignant plasma cells in the
absence of exogenous chemotactic stimuli. In others, chemotaxis
might be induced by several chemokines, mainly SDF and Mip3.
Furthermore the analysis of chemokine production from
malignant plasma cells revealed a heterogeneous pattern.
These observations indicate that myeloma cells have variable
pattern of expression of chemokine receptors and displayed a
marked capability to migrate in vitro, this property being more
evident in patients with progressive disease or in patients with the
leukemic form of the disease.
058
Expression of receptor activator of NF-κB ligand
(RANKL) on bone marrow plasma cells from patients
with multiple myeloma correlates with osteolytic bone
disease
Ulrike Heider, Christian Jakob, Ivana Zavrski, Corinna
Langelotz, Claudia Fleissner, Jan Eucker, Kurt Possinger,
Lorenz C. Hofbauer, Orhan Sezer
Department of Hematology and Oncology, Universitätsklinikum
Charité, Berlin and Department of Gastroenterology, Endocrinology
and Metabolism, Philipps Universität Marburg, Germany
Increased bone resorption is a hallmark of multiple myeloma and
is due to excessive osteoclast activation. The recently
characterized receptor activator of NF-κB ligand (RANKL) is a
key mediator of osteoclastogenesis and plays a crucial role in
bone destruction in malignant bone disease. Myeloma cells
induce RANKL expression in bone marrow stromal cells.
Recently, we detected RANKL protein on humane myeloma
cells using flow cytometry and immunocytochemistry. In this
study, we analyzed the association of RANKL expression on
plasma cells and osteolytic bone disease in patients with multiple
myeloma. Flow cytometry was performed on bone marrow
samples derived from controls and 50 multiple myeloma patients
with (n=35) or without (n=15) osteolytic bone lesions on
radiography. Plasma cells were identified as CD38++/CD138+
cells. The mean fluorescence index for RANKL on the surface of
bone marrow plasma cells was correlated with the bone status of
the patients. Bone marrow plasma cells from controls showed no
or only a very weak expression of RANKL, the median mean
fluorescence index (MFI) was 6. In contrary, RANKL could be
detected on bone marrow plasma cells from all patients with
multiple myeloma, median MFI was 47. The difference in MFI
for RANKL expression of bone marrow plasma cells from
controls and myeloma patients was highly significant (P <
0.0005). Myeloma patients with osteolytic bone lesions showed a
significantly higher surface expression of RANKL (median
MFI=60, range 16-2494) compared to patients without osteolysis
(median MFI=16, range 6-229) (P < 0.0005). These findings
show that the level of expression of RANKL on bone marrow
plasma cells correlates with the bone status in multiple myeloma
and underscore the clinical relevance of the RANKL expression
by myeloma cells.
S114