Biological Subgroups of Chronic Lymphocytic Leukemia with Isolated 13q14 Deletion
Prashanti Reddy, Bashar Dabbas, Dianne Keen-Kim, Yin Xu. Genoptix Medical Lab, A Novartis Company, Carlsbad
Background: Deletion of 13q14 is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL). While monoallelic 13q14 deletion as a single abnormality is associated with good prognosis, the significance of biallelic deletion has been controversial. Recent studies suggest that CLL with higher percentages of 13q- nuclei is associated with a more aggressive clinical course. To further our understanding of the clinical relevance of subgroups of 13q- CLL, we have examined a consecutive series of CLL with 13q14- as the sole cytogenetic abnormality.
Design: 500 CLL cases with complete karyotyping/FISH and IgVH studies were retrieved from our database over a 2-year period: 235 cases with isolated 13q14 deletion and 265 cases with normal karyotype/FISH. Clinicopathologic parameters obtained for those cases included age, sex, CBC, bone marrow (BM) tumor burden, Zap-70 and CD38 expression by flow cytometry, and IgVH status. In addition, the percentage of 13q- nuclei in 200 cells by FISH was also obtained for comparative analysis.
Results: 175 cases showed monoallelic 13q- and 60 biallelic 13q-. There was no significant difference in age, sex, WBC (mean: 32k/uL), hemoglobin (mean: 13.4g/dL), platelet count (mean: 287k/uL), BM tumor burden (mean: 49%), CD38 expression, and Zap-70 level between the two groups. However, IgVH hypermutation was more frequent in biallelic (90%) than in monoallelic (70%; p=0.004) or in normal FISH cases (60%; p<0.0001). When grouping cases by percentage of 13q-, the average BM tumor burden was found to be significantly higher in cases with >65% 13q- (70%) than in those with ≤65% 13q- (38%; p=<0.0001) or with normal FISH (46%; p=0.0001). Cases with ≤65% 13q- had a significantly lower tumor burden (38%) compared to those with normal FISH (46%; p=0.0229). WBC also was higher when 13q- was >65% (53k vs. 20k; p=<0.0001). The IgVH status was not significantly different between the two groups (≤65%13q- and >65%13q-), nor were CD38 and ZAP-70 expression levels. However, when compared with normal FISH cases, IgVH hypermutation was more frequent in cases with ≤65% 13q- (78% vs. 60%; p=0.0003) as well as in >65% 13q- (72% vs. 60%; p=0.05).
Conclusions: CLL with >65% 13q- is more advanced at initial diagnosis with higher WBC and marrow infiltrate. The adverse effect of higher percentage of 13q- is independent from IgVH, ZAP-70, and CD38. Although CLLs with monoallelic and biallelic 13q- show a similar clinical presentation, the biallelic 13q- CLL correlates with IgVH hypermutation, suggesting a biologically distinct subgroup.
Tuesday, March 20, 2012 11:15 AM
Platform Session: Section C, Tuesday Morning