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Journal Article

Molecular map of chronic lymphocytic leukemia and its impact on outcome

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Kretzmer,  Helene
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Meissner,  Alexander
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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NatureGenet_Knisbacher et al_2022.pdf
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Citation

Knisbacher, B. A., Lin, Z., Hahn, C. K., Nadeu, F., Duran-Ferrer, M., Stevenson, K. E., et al. (2022). Molecular map of chronic lymphocytic leukemia and its impact on outcome. Nature Genetics. doi:10.1038/s41588-022-01140-w.


Cite as: https://hdl.handle.net/21.11116/0000-000A-EB6C-5
Abstract
Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the ‘CLL map,’ we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. Discovery of new gene expression subtypes further subcategorized this neoplasm and proved to be independent prognostic factors. Clinical outcomes were associated with a combination of genetic, epigenetic and gene expression features, further advancing our prognostic paradigm. Overall, this work reveals fresh insights into CLL oncogenesis and prognostication.