Clinical and biologic implications of recurrent genomic aberrations in myeloma
Issue date
2003Author
Fonseca, Rafael
Blood, Emily
Harrington, David
Oken, Martin M.
Kyle, Robert A.
Dewald, Gordon W.
Van Ness, Brian
Van Wier, Scott A.
Henderson, Kimberly J.
Bailey, Richard J.
Greipp, Philip R.
Suggested citation
Fonseca, Rafael;
Blood, Emily;
Rué i Monné, Montserrat;
Harrington, David;
Oken, Martin M.;
Kyle, Robert A.;
...
Greipp, Philip R..
(2003)
.
Clinical and biologic implications of recurrent genomic aberrations in myeloma.
Blood, 2003, vol. 101, núm. 11, p. 4569-4575.
https://doi.org/10.1182/blood-2002-10-3017.
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Show full item recordAbstract
Nonrandom recurrent chromosomal abnormalities
are ubiquitous in multiple myeloma
(MM) and include, among others,
translocations of the immunoglobulin
heavy chain locus (IgH). IgH translocations
in MM result in the up-regulation of
oncogenes, and include more commonly
t(11;14)(q13;q32), t(4;14)(p16;q32), and
t(14;16)(q32;q23). Based on the recurrent
nature of these translocations and their
finding since the early stages of the
plasma cell (PC) disorders, we hypothesized
that they would confer biologic
and clinical variability. In addition, deletions
of 13q14 and 17p13 have also been
associated with a shortened survival. We
used cytoplasmic Ig–enhanced interphase
fluorescent in situ hybridization to detect
deletions (13q14 and 17p13.1), and translocations
involving IgH in 351 patients
treated with conventional chemotherapy
entered into the Eastern Cooperative Oncology
Group clinical trial E9486/9487.
Translocations were frequently unbalanced
with loss of one of the derivative
chromosomes. The presence of t(4;
14)(p16;q32) (n 42; 26 vs 45 months,
P < .001), t(14;16)(q32;q23) (n 15; 16 vs
41 months, P .003), 17p13 (n 37; 23
vs 44 months, P .005), and 13q14
(n 176; 35 vs 51 months, P .028) were
associated with shorter survival. A strati-
fication of patients into 3 distinct categories
allowed for prognostication: poor
prognosis group (t(4;14)(p16;q32), t(14;
16)(q32;q23), and 17p13), intermediate
prognosis ( 13q14), and good prognosis
group (all others), with median
survivals of 24.7, 42.3, and 50.5 months,
respectively (P < .001). This molecular cytogenetic
classification identifies patients
into poor, intermediate, and good risk
categories. More importantly it provides
further compelling evidence that MM is
composed of subgroups of patients categorized
according to their underlying
genomic aberrations.