Haematologica 2003 - Supplements

clusters were found, the first was composed of gains of
chromosomes 3, 5, 7, and 9, as well as hyperdiploidy, and the
second of losses of chromosome 1, 4, 8, 13, 14, 16, 17, 20, 21, 22
and hypodiploid karyotypes. Moreover, a third group including
those cases with "more than triploid karyotype” was observed,
possibly conforming an independent cytogenetic subgroup.
Further studies will focus in the relationship between these
chromosomal abnormality patterns, clinical parameters and
outcome.
038
AML/MDS-associated cytogenetic abnormalities in
multiple myeloma and monoclonal gammopathy of
undetermined significance: evidence for de novo
occurrence and stem cell involvement of del(20q) as a
sole change
T Nilsson1, L Nilsson2,3, S Lenhoff3, L Rylander4, I
Åstrand-Grundström2, B Stömbeck1, M Höglund1, I
Turesson5, J Westin3, F Mitelman1, SE Jacobsen2 and B
Johansson1
1Department of Clinical Genetics, Lund University Hospital,
Sweden; 2Department of Stem Cell Biology, Lund University
Hospital, Sweden; 3Department of Hematology, Lund University
Hospital, Sweden; 4Department of Occupational and
Environmental Medicine, Lund University Hospital, Sweden; and
5Department of Hematology, Malmö University Hospital, Sweden
The plasma cell dyscrasias multiple myeloma (MM) and
monoclonal gammopathy of undetermined significance (MGUS)
are cytogenetically characterized by various translocations
involving 14q32, -13 or del(13q), and trisomies of chromosomes
3, 7, 9, 11, and 15. However, karyotypic patterns characteristic
for acute myeloid leukemia (AML) and myelodysplastic
syndromes (MDS), eg hypodiploidy with total or partial losses of
chromosomes 5 and 7, may occasionally also occur in the setting
of plasma cell dyscrasias. In most instances, such AML/MDSassociated
cytogenetic features signify the development of
therapy-related malignancies, in particular t-AML/t-MDS in MM
patients previously treated with alkylating agents. In a few
instances, however, “myeloid” chromosomal changes are
detected in untreated plasma cell disorders without any
morphologic features of AML/MDS. Whether these aberrations
have arisen in myeloid precursor cells, heralding an ensuing
myeloid malignancy, or whether they exist in the MM/MGUS
cells is unknown. In order to characterize the “myeloid”
abnormality patterns in MM and MGUS patients, we have
ascertained and reviewed all 123 MM and 25 MGUS cases as
well as all 19 t-AML/t-MDS occurring after previous
chemotherapy for MM cytogenetically analyzed in our
department. Among these, 67 (54%) MM, 7 (28%) MGUS, and
16 (84%) t-AML/t-MDS were karyotypically abnormal, with 7
(10%) MM and 2 (29%) MGUS displaying “myeloid”
abnormalities, ie +8 (one case) and 20q- (eight cases), without
any evidence for AML/MDS. In the MGUS case, interphase
fluorescence in situ hybridization analyses with a probe for 20q12
revealed the presence of the del(20q) in all cell populations
investigated (CD34+, CD34+CD38-, CD34+CD38+, CD34-,
CD19+, CD15+, and CD3+). The present data indicate that
del(20q) as a sole anomaly occurs as a de novo aberration in
approximately 10% of karyotypically abnormal MM/MGUS
cases and also strongly suggest that it arises at the stem cell level.
039
Cytogenetics, Interphase and Multiplex FISH of Multiple
Myeloma.
Christine J. Harrison, G. Reza Jalali, Ashraf H. Ibrahim, Kim
H. Orchard, Fiona M. Ross
Leukaemia Research Fund Myeloma Cytogenetics Database,
Cancer Sciences and Human Genetics Divisions, University of
Southampton, Southampton, UK.
Translocations involving the immunoglobulin heavy chain gene
(IGH) at 14q32 have been proposed to be primary abnormalities
in myeloma. Monosomy or deletions of chromosome 13 have
been associated with a poor prognosis. Interphase fluorescence in
situ hybridisation (FISH) has now become the method of choice
for the detection of these abnormalities due to the difficulties of
conventional cytogenetic analysis. The limitation of interphase
FISH is that interpretation of karyotypes is restricted to the
specific chromosomal sites under investigation and important
abnormalities of these regions may be masked within complex
karyotypes and those with very high chromosome numbers.
However, even when conventional cytogenetics is successful, the
complexity of the karyotypes often precludes accurate
characterisation. The complementary application of 24 colour
FISH (M-FISH), cytogenetics and FISH with specific probes can
resolve many of the problems of interpretation.
We have applied these techniques to a series of 19 myeloma
patients with abnormal karyotypes. In agreement with other
studies, cytogenetics and M-FISH revealed that chromosomes 3,
5, 7, 9, 11, 15, 19 and 21 were most frequently gained in
hyperdiploid karyotypes and chromosomes 13 and 22 were often
lost. Although no new recurring structural chromosomal changes
were identified in this small series, a high incidence of complex
abnormalities were observed in all cases. Multiple
rearrangements involving chromosome 1 were observed in 17/19
cases. Other frequently occurring structural changes involved
chromosomes 5, 6, 7, 8, 14 and 16, many of which were only
visible by M-FISH. Cryptic abnormalities of chromosomes X and
Y were also shown by M-FISH only. Metaphases from cases with
apparent discrepancies between the cytogenetics/M-FISH and
interphase FISH were re-hybridised with the IGH or locusspecific
chromosome 13 probes. This revealed cryptic and
complex involvement of chromosome 14 with a range of partners,
including chromosomes 1, 2, 7, 8 and 12 and a cryptic
chromosome 13 deletion. Our findings have confirmed that
accurate interpretation of karyotypes benefits from the
complementary application of these techniques. This approach
facilitates the search for new chromosomal abnormalities with
clinical or prognostic significance and helps to identify
significant patterns of genetic change, which will further our
understanding of the role of genetics in the development and
progression of myeloma.
040
IN SEARCH FOR NEW RECURRENT CHROMOSOME
BREAKPOINTS IN MULTIPLE MYELOMA
Blanca Fernández, Borja Saez, Miguel Urioste, Javier
Benítez, Maria D. Odero, Jose I. Martín-Subero, Reiner
Siebert, M. José Calasanz, Juan C. Cigudosa
Cytogenetics Unit, Centro Nacional de Investigaciones
Oncológicas, Madrid, Spain; Departamento de Genética,
Universidad de Navarra, Pamplona, Spain; and Institute of Human
Genetics, University Hospital Schleswig-Holstein Campus Kiel,
Kiel, Germany.
The use of advanced molecular cytogenetic techniques, as
Spectral Karyotyping (SKY), on multiple myeloma (MM) has
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