Two distinct molecular subtypes of chronic lymphocytic leukemia give new insights on the pathogenesis of the disease and identify novel therapeutic targets

Abstract

Biopsy samples of lymph nodes from 38 patients with CLL were analyzed. We found differential expression in 1092 genes in two different subgroups: 418 overexpressed in one subgroup and 674 in another. Molecular pathways identified in one subgroup appear to be characterized by greater dependence of signaling by cytokines and activation of the NFkB pathway, while in the other seem to depend on cell cycle. Despite having found a differential expression between both subgroups, none of these genes reached FDR < 0.25. We have not found significant association with survival or any prognostic factors. Analysis of the differences between normal lymph node and CLL in 253 genes with difference in the intensity of expression revealed upregulated genes different to BCR: CD40, TCL1, IL-7, and PAX5. Using large-scale molecular analysis, we may obtain information about molecular mechanisms of CLL pathogenesis and may contribute to the identification of new therapeutic targets.

Keywords::

• Chronic lymphocytic leukemia
• gene-expression profile
• molecular subtype

Acknowledgements

We thank CNIO Tumor Biobank for providing the biological samples and associated clinical data included in this study. This study was supported by a grant from the Spanish Association Against Cancer (AECC).

Potential conflict of interest

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Supplementary material available online

The molecular pathways in which enrichment identified gene clusters