Abstract 3925

According to The European Myeloma Network(1), FISH analysis of plasma cell myeloma (multiple myeloma, or MM) should be performed on samples enriched for plasma cells or an assay that allows for identification and study of plasma cells apart from other cells should be utilized. We enriched 400 bone marrow samples sent to our laboratory from May-September 2010 using CD138 antibody microbeads for plasma cells and then performed FISH utilizing probes for CEP3, CEP7, CEP9, CEP11, IgH breakapart, IgH/CCND1 (11;14), IgH/MAF (14;16), IgH/FGFR3(4;14), Rb1/13q, and TP53/CEP17. The genotypic profiles were then compared to the immunophenotypic profiles of monoclonal plasma cells derived from flow cytometric immunophenotyping for the following antibodies: CD38, CD19, CD56, CD117, CD20, HLA DR, CD45 and CD10.

We identified genetic abnormalities in 90.6% (184/203) of the samples with monoclonal plasma cell percentages of 0.1% or more as detected by concurrent flow cytometric analysis. The most common identified genetic abnormality was aneuploidy {55.5% (222/400)}, either as a sole finding or in combination with translocations or gene loss. The aneuploid samples were further found to be hyperdipoid {23.75% (95/400)}, hypodiploid {15.75% (63/400)}, or polypoid {16.00% (64/400)}. IgH rearrangement was the seond most common abnormality and was seen in 30.2% of the 400 cases. The IgH rearrangements and frequencies were as follows: 11.25% (45/400) with t(11;14), 5.5% (22/400) with t(4;14), 3.0% (12/400) with 14;16, and 10.5% (42/100) with IgH translocation with partners unknown. Deletion of chromosome 13q/monosomy 13 was observed in 26% (104/400) of cases. This was an isolated finding in 3/400 (0.75%), observed with aneuploidy in 71/400 (17.75%), and seen in combination with IgH rearrangement in 64/400 (16.0%). There was a strong association between del (13q14) and IgH rearrangement, especially with t(4;14) and t(14;16). Loss of TP53 was observed in 3.8% (15/400) of cases. This was an isolated finding in 0/400 (0%), observed with aneuploidy in 14/400 (3.5%), and seen in combination with IgH rearrangement in 8/400 (2%).

We explored the relationship between identified genetic abnormalities and respective immunophenotypic findings for the cases. Our results showed that t(4;14) was significantly associated with expression of CD56 (17/17 positive, 100%) and the absence of CD117 (76.5% negative, 13/17) and CD20 (82.4% negative, 14/17). On the other hand, t(14;16) was only rarely seen in combination with CD56 expression (88.9% negative, 8/9) or CD20 expression (100% negative, 9/9), but was highly associated with CD117 expression (66.7% positive, 6/9). t(11;14) was associated with CD20 expression (21.9% positive, 7/32), CD56 expression (34.4% positive, 11/32), and CD117 expression (37.5% positive, 12/32). Additionally, our results found that both CD56 and CD117 expression correlate with aneuploidy.


No relevant conflicts of interest to declare.

FonsecaR. Genetics and cytogenetics of multiple myeloma: a workshop report.
Cancer Res.

Author notes


Asterisk with author names denotes non-ASH members.