Haematologica 2003 - Supplements

chromosomal losses were found. The most frequent abnormalities
were gains of chromosomes 9 and 15, which were observed in 7
of the 13 patients (54%). Chromosomal gains were detected in all
evolving and non-evolving patients with CGH imbalances. In
contrast, chromosomal losses were observed in 5 of the 7 patients
(71%) with evolving SMM and in only one of the 8 patients
(16%) with non-evolving SMM. The most recurrent changes in
evolving SMM were gains of 1q (57%) and deletion of 8p, 13q,
14q and 16q (43%). Patients with non-evolving SMM showed
recurrent gains on 3p, 7, 11q and 18 (33%).
Conclusions: The most recurrent changes in SMM consist of
gains of chromosomes 9 and 15. Evolving SMM displays
multiple chromosomal imbalances with gains and losses
(including deletion of chromosome 13), findings consistent with
the characteristic chromosomal abnormalities commonly seen in
patients with symptomatic MM. In contrast, in non-evolving
SMM chromosomal losses are uncommon. Therefore, althought
the number of patients studied is low, the two subsets of SMM
seem to have different cytogenetic patterns, which are associated
with a different natural history.
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Gene expression profiling of multiple myeloma reveals
molecular portraits in relation to the pathogenesis of
the disease
Florence Magrangeas,1 Hervé Avet-Loiseau,1 Olivier
Decaux,1 Rémi Houlgatte‚2 and Stéphane Minvielle1
1INSERM U463, University Hospital, Nantes, France2INSERM
ERM206, Centre d’Immunologie de Marseille-Luminy, Marseille,
France
Although multiple myeloma (MM) is a unique entity, a marked
heterogeneity is actually observed among the patients, which has
been first related to immunoglobulin (Ig) types and light chain
subtypes, and more recently to chromosomal abnormalities. In
order to further investigate this genetic heterogeneity, we
analyzed gene expression profiles of 92 primary tumors
according to their Ig types and light chain subtypes with DNA
microarrays. Several clusters of genes involved in various
biological functions such as immune response, cell cycle control,
signaling, apoptosis, cell adhesion and structure significantly
discriminated IgA- from IgG-MM. Genes associated with
inhibition of differentiation and apoptosis induction were upregulated
while genes associated with immune response, cell
cycle control and apoptosis were down-regulated in IgA-MM.
According to the expression of the 61 most discriminating genes,
BJ-MM represented a separate subgroup that did not express
either the genes characteristic of IgG-MM, or those of IgA-MM
at a high level. This suggests that transcriptional programs
associated to the switch could be maintained up to plasma cell
differentiation. Several genes whose products are known to
stimulate bone remodeling discriminate between κ and λ MM.
One of these genes, Mip-1αwas overexpressed in the κ subgroup.
In addition we established a strong association (P=.0001)
between κ subgroup expressing high levels of Mip-1α and active
myeloma bone disease. This study shows that DNA microarrays
enable to perform a molecular dissection of the bioclinical
diversity of MM and provides new molecular tools to investigate
the pathogenesis of malignant plasma cells.
046
Cytogenetic Analysis For Chromosome 13 Abnormality
In Multiple Myeloma: Experience From A Cancer Center
In India
Atul Sharma, Shawgi S, Lalit Kumar, Sujata Mohanty,
Vinod Kochupillai
Institute Rotary Cancer Hospital, All India Institute of Medical
Sciences, New Delhi, India
Introduction: Chromosomal abnormalities are rapidly emerging
as one of the important prognostic factor in Multiple Myeloma
(MM). The most common numerical abnormality reported is in
relation to chromosome 13 ( 13q- or deletion of chromosome 13).
It has been demonstrated to carry independent poor prognosis.
However, there are no Indian data as regard to incidence of
chromosome 13 abnormality in Indian patients. Material and
Method: From March 2000 to May 2002, 22 newly diagnosed
patients were enrolled onto this study to find out incidence and
significance of chromosomal 13 abnormality in MM patients.
Cytogenetic analysis on bone marrow aspiration was done using
Trujillo’s method with some modification. Patients
characteristics: Median age- 53.5 years (32-75 years), Sex- males
15, Stage distribution- IIIA- 16, and IIIB- 6 patients. Seventeen
patients had positive serum “M” band ( median level 2.45gm/dl).
Five patients had pure light chain myeloma. Median bone marrow
plasma cells were 60%. Results: Of the 22 patients 16 had
adequate analyzable metaphases, 2 had few and overlapped
metaphases, and in 4 patients no metaphases were found. Median
number of metaphases analysed were 9.5. Chromosome 13
abnormality in the form of deletion was seen in only one patient.
This patient achieved PR to melphalan based therapy and is
alive after follow up of for 2.5. Since, only one was detected to
have chromosomal abnormality no meaningful correlation with
M band level, plasma cell percentage, stage at diagnosis, and its
prognostic significance was possible. As per literature 30-40% of
patients will have chromosomal 13 abnormality. The possible
reasons for low detection rate could be: only 16 patients had
analyzable metaphases, median number of metaphases analyzed
were low ( ?reflecting low mitotic index), and in many samples
G banding resolution was poor. Conclusion- Conventional
cytogenetics is a useful investigation modality for MM patients.
However, we feel that further refinement of the technique is
required in developing centers like ours so as to increase the yield
of metaphases. This will than reflect the true incidence of
chromosomal abnormality and its prognostic significance.
Alternatively synchronization techniques or FISH should be
employed.
047
COMPARISON OF THE PROGNOSTIC IMPACT OF
CHROMOSOME 13 DELETION DETECTED BY
CONVENTIONAL CYTOGENETICS vs FISH ANALYSIS
IN MULTIPLE MYELOMA PATIENTS: AN SPANISH GEM
GROUP STUDY.
Norma C. Gutiérrez, Ana Rasillo, Belén Gil, María L.
Martín, José M. Sayagués , Isabel Isidro, Jesús M.
Hernández, Juan J. Lahuerta, Jesús F. San Miguel
On behalf of GEM group.
Introduction: Abnormalities on chromosome 13 (13q- and
monosomy) have been associated with unfavorable prognosis in
patients with multiple myeloma (MM). The different prognosis
significance of 13 abnormalities depending on the method of
detection, conventional karyotype or FISH analysis, remains a
matter of controversy.
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