Anaplastic Multiple Myeloma Is Associated with High-Risk Molecular Cytogenetic Abnormalities
DT Kim, H Chang. University Health Network and University of Toronto, Toronto, Canada
Background: The WHO classification recognizes anaplastic multiple myeloma (AMM) as a rare morphologic variant characterized by pleomorphic multinucleate plasma cells with prominent nucleoli. AMM is associated with extramedullary infiltrates and an adverse prognosis but little is known about the underlying molecular cytogenetic abnormalities. We systematically analyzed 11 cases of AMM and compared their molecular cytogenetic features with 180 newly diagnosed non-anaplastic MM.
Design: AMM cases were morphologically identified according to WHO criteria, their clonal plasma cells immunophenotyped and clinical features reviewed. The clonal plasma cells from bone marrow aspirates were examined by interphase fluorescence in situ hybridization (FISH) for myeloma-related genetic abnormalities. The FISH analysis included probes for translocations t(11;14) (cyclin D1), t(4;14) (FGFR3), deletions 13q14 and 17p(p53), and amplifications of 1q21(CKS1B).
Results: There were 7 males and 4 females with a median age of 61 years (range, 39-70). Four patients had IgA, 3 IgG kappa, and 4 light chain only. The median bone marrow plasmacytosis was 85% (range, 40-100%). Interphase FISH detected CKS1B amplifications (3-8 FISH signals) in 10 (91%) of 11 cases, the median percentage of myeloma cells with CKS1B amplification was 80% (range, 40-100%). FISH detected hemizygous p53 deletions in 5/11, 13q deletions in 4/11, t(4;14) in 4/11, and t(11;14) in 2/11 cases. One case had 4 coexisting genetic abnormalities, 5 cases had 3 abnormalities, and the remaining cases had 1-2 abnormalities. In comparison, the newly diagnosed MM had CKS1B amplification, p53 deletion, 13q deletion, t(4;14) and t(11;14) in 34%, 11%, 41%, 13% and 13% respectively. AMM had significantly higher prevalence of CKS1B amplification (p=0.0003), p53 deletion (p=0.001) and t(4;14) (p=0.004) than that of non-anaplastic MM.
Conclusions: AMM represents a subset of MM frequently harboring high-risk genomic aberrations, particularly, CKS1B amplification. The high prevalence of CKS1B amplification, p53 deletion, and t(4:14) may indicate genetic instabilities of AMM cells resulting in a more aggressive behavior of the disease.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 208, Wednesday Morning