BACKGROUND: Chronic lymphocytic leukemia (CLL) is typically regarded as an 
indolent B-cell malignancy. However, there is wide variability with regards to 
need for therapy, time to progressive disease, and treatment response. This 
clinical variability is due, in part, to biological heterogeneity between 
individual patients' leukemias. While much has been learned about this 
biological variation using genomic approaches, it is unclear whether such 
efforts have sufficiently evaluated biological and clinical heterogeneity in 
CLL.
METHODS: To study the extent of genomic variability in CLL and the biological 
and clinical attributes of genomic classification in CLL, we evaluated 893 
unique CLL samples from fifteen publicly available gene expression profiling 
datasets. We used unsupervised approaches to divide the data into subgroups, 
evaluated the biological pathways and genetic aberrations that were associated 
with the subgroups, and compared prognostic and clinical outcome data between 
the subgroups.
RESULTS: Using an unsupervised approach, we determined that approximately 600 
CLL samples are needed to define the spectrum of diversity in CLL genomic 
expression. We identified seven genomically-defined CLL subgroups that have 
distinct biological properties, are associated with specific chromosomal 
deletions and amplifications, and have marked differences in molecular 
prognostic markers and clinical outcomes.
CONCLUSIONS: Our results indicate that investigations focusing on small numbers 
of patient samples likely provide a biased outlook on CLL biology. These 
findings may have important implications in identifying patients who should be 
treated with specific targeted therapies, which could have efficacy against CLL 
cells that rely on specific biological pathways.