Biology Reference
In-Depth Information
15.1 Multiple Myeloma
Multiple Myeloma (MM) is a neoplastic clonal proliferation of plasma cells
occurring multifocally within the bone marrow (Swerdlow et al.
2008
). At present,
MM accounts for approximately 1 % of cancers, 15 % of hematopoietic neo-
plasms, and 20 % of deaths from hematologic malignancies (Jemal et al.
2010
).
Clinical manifestations include the presence of serum M-protein, hypercalcemia,
renal insufficiency, anemia, and bone lesions (Kyle and Rajkumar
2004
). Despite
therapeutic advances, the disease remains incurable at present with a median
survival of around 4 years (Kumar et al.
2008
).
Monoclonal gammopathy of undetermined significance (MGUS) is a prema-
lignant state of MM with an estimated prevalence of 3.2 % in patients above
50 years of age (Wadhera and Rajkumar
2010
). MGUS is characterized by a
monoclonal plasma cell proliferation within the bone marrow without end-organ
damage (International Myeloma Working Group
2003
). The risk of progression of
MGUS to MM or related disorders is about 1 % per year (Kyle et al.
2002
).
15.2 Genetic Abnormalities in Multiple Myeloma
Complex genetic aberrations in the form of either numerical and/or structural
chromosomal abnormalities are ubiquitous in MM (Avet-Loiseau et al.
1999
;
Nishida et al.
1997
; Smadja et al.
1998
,
2001
; Mohamed et al.
2007
; Drach et al.
1995
). In fact, several genetic and molecular subtypes of MM with distinct
clinicopathological features have been identified (Fonseca et al.
2009
). At the top
hierarchical level, MM can be divided into hyperdiploid and non-hyperdiploid
subtypes (Smadja et al.
1998
,
2001
; Carrasco et al.
2006
). Hyperdiploid MM
(H-MM) is characterized by trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19 and
21, and has a low prevalence of primary immunoglobulin heavy chain (IgH)
translocations. This is in contrast to non-hyperdiploid MM (NH-MM), which
encompasses hypodiploid, pseudodiploid, and near tetraploid MM and is strongly
associated with IgH translocations (Fonseca et al.
2003
). The identification of
unique gene expression signatures associated with these genetic subtypes
provides further support that the H-MM and NH-MM categories are biologically
distinct (Bergsagel et al.
2005
; Zhan et al.
2006
). This dichotomy into H-MM
and NH-MM is also seen in MGUS (Chng et al.
2005
; Brousseau et al.
2007
),
indicating that these distinct pathogenetic pathways arise early in the course of
the disease.
