Haematologica 2003 - Supplements

3. Immunobiology
053
IMMUNOPHENOTYPE PROFILE IN MONOCLONAL
GAMMOPATHY UNDETERMINED SIGNIFICANCE AND
MULTIPLE MYELOMA
Lemes A, Golvano E, de la Iglesia S, Santana A*, Gómez
MT, Jiménez S. and Molero T.
Department of Hematology. Hospital Universitario de Gran Canaria
Dr Negrín. Las Palmas de Gran Canaria.* Research Unit of La
Laguna University. Santa Cruz de Tenerife. Spain.
Monoclonal gammopathy of undetermined significance (MGUS)
is the most common plasma cell dyscrasia occurring in up to 10%
of the population over age 75. Differential diagnosis between
myeloma multiple (MM) and MGUS is sometimes uncertain
especially in early phases of MM, and the distinct
immunophenotype of plasma cells in each one can be helpful in
order to reach a correct diagnosis.
The aim of this study was to describe the immunophenotype of
bone marrow plasma cells (BMPC) in MGUS and MM.
Methods: Bone marrow samples from 57 patients with MM and
28 patients with MGUS were evaluated by flow cytometry (FC)
after incubation with the following monoclonal antibodies:
CD138FITC/CD56PE/CD19TC/CD38APC. The plasma cells
were identified as CD38++/CD138 positive cells and a live gate
acquisition strategy was performed.
Results: Four plasma cells subpopulations could be identified in
the bone marrow (Table 1): CD19+/CD56-; CD19-/CD56+;
CD19+/CD56+ and CD19-/CD56-.
Table 1
CD19+/CD5
6- (%)
CD19-
/CD56+ (%)
CD19+/CD5
6+ (%)
CD19-
/CD56-
(%)
MM 26 68 26 23
MGU
68 68 39 18
S
% of patients showing each immunophenotype.
The percentage of plasma cells displaying a particular phenotype
was different for each pathology. So the CD19-/CD56+
expression in >70% of BMPC was found in 40% of MGUS and
in 90% of MM. The 53% of MGUS displayed a CD19+/CD56-
phenotype in a high percentage (>65%) of all BMPC, while a
40% of cells with this phenotype was found in MM.
CD19+/CD56+ coexpression was observed in both entities but
the number of BMPC displaying this phenotype in MGUS was
lower than in MM. Otherwise the CD19-/CD56- subpopulation
was higher in MGUS than in MM.
The follow-up of nine patients with MGUS (mean 28 months) (R
8-77months) demonstrated an evolution to MM in two of them
22 and 13 months after diagnosis. The plasma cells in these cases
showed a CD19-/CD56+ original immunophenotype in the 100%
of the cells.
Surprisingly the patient with 77 evolution months did not show
any normal immunophenotype plasma cell (15% CD19-/CD56+;
17% CD19+/CD56+ and 68% CD19-/CD56-). Most of patients
with non-evolutionated MGUS showed a high percentage (>68%)
of CD19-/CD56- plasma cells. This fact could be of prognosis
importance in the MGUS evolution.
Discussion. Plasma cells in MGUS and MM showed a
heterogeneous immunophenotype. Unlike other studies we
observed a normal plasma cell population in MM. Nevertheless,
32% of MGUS cases displayed only an aberrant plasma cell
phenotype.
In summary, our data showed that flow cytometric analysis can
be helpful in the differential diagnosis of MGUS and MM but we
did not find a single parameter for this purpose.
The CD56-/CD19- population in MGUS patients and their
prognostic significance warrant further investigation.
054
Immunophenotypic differences between clonal plasma
cells from MGUS (monoclonal gammopathy of
undetermined significance), MM (multiple myeloma)
and PCL (plasma cell leukemia)”
M Pérez de Andrés1,2, M Martin-Ayuso1,2, J Almeida1,2,
MA García-Marcos3, MI González Fraile4, MJ Moro4, J
Galende5, MJ Rodríguez6, JF San Miguel2,3, A Orfao1,2
1- Servicio de Citometría. Univ. Salamanca. 2.-Centro de
Investigación del Cáncer. Univ. de Salamanca. 3-Servicio de
Hematología. Hosp. Univ. de Salamanca. 4-Servicio de
Hematología. Hospital Virgen Blanca (León). 5- Servicio de
Hematología. Hospital del Bierzo (León). 6-Servicio de
Hematología. Hospital Nstra Sra Sonsoles (Ávila). SPAIN
Previous studies have rported on the existence of important
phenotypic differences between normal and clonal plasma cells
(PC). In contrast, few markers have been shown to be
differentially expressed in clonal PC from patients with MGUS
(monoclonal gammopathies of undetermined significance) as
compared to MM (multiple myeloma) and PCL (plasma cell
leukemia).
In the present study, we have comparative analyzed the
expression of surface markers on clonal PC from MGUS, MM
and PCL patients as well as normal PC from the same individuals
and an age-matched healthy group of donors. Our major interest
focused on the study of phenotypic markers of clonal PC that are
involved in their interactions with the bone marrow
microenvironment, these including costimulatory (CD40, CD80,
CD86) and adhesion molecules (CD38, CD56, CD138, CD106),
cytokine receptors (CD126, CD130), HLA molecules (HLA-Iα
and β2-microglobulin) and the Fas receptor (CD95).
Bone marrorrow PC from total of 30 MGUS, 27 MM, 4 PCL (all
newly diagnosed untreated patients) and 5 normal individuals
were analyzed by flow cytometry specifically gating on
CD38high and CD138+ cells. In all cases, antigen expression
was evaluated as the mean fluorescence intensity (MFI).
Our results confirm that PC from normal BM display identical
phenotypic features to those of normal PC from cases with
MGUS. They were constantly positive for CD138, CD38, CD40,
HLA-Iα and β2-microglobuline, while they lacked on the
expression of the IL-6Rα-chain (CD126) and CD80 and
displayed variable reactivity for CD130, CD86 and CD56 (Table
1).
Upon comparing this phenotype of normal PC with that of PC
from patients with monoclonal gammopathies (MG), significant
differences were found for all markers tested, except for CD138,
CD130, CD80 and CD106. A detailed analysis of these
differences shows that clonal PC from patients with MG
constantly displayed abnormally higher levels of CD56, CD86
and CD126, together with low amounts of CD38, independently
of the diagnostic subgroup. In addition, HLA-Iα and β2-
microglobulin were expressed at abnormally high levels in
MGUS and to a lower extent in MM but decreased or normal in
PCL; in turn CD40, expression was abnormally decreased in MM
and PCL but not in MGUS, whereas reactivity for CD95 was only
detected in PC from PCL cases. The exact phenotypes of normal
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