Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.
In: Nature Communications, Jg. 12 (2021-09-13), Heft 1, S. 1-18
academicJournal
Zugriff:
Knowledge of the genomic landscape of chronic lymphocytic leukemia (CLL) grows increasingly detailed, providing challenges in contextualizing the accumulated information. To define the underlying networks, we here perform a multi-platform molecular characterization. We identify major subgroups characterized by genomic instability (GI) or activation of epithelial-mesenchymal-transition (EMT)-like programs, which subdivide into non-inflammatory and inflammatory subtypes. GI CLL exhibit disruption of genome integrity, DNA-damage response and are associated with mutagenesis mediated through activation-induced cytidine deaminase or defective mismatch repair. TP53 wild-type and mutated/deleted cases constitute a transcriptionally uniform entity in GI CLL and show similarly poor progression-free survival at relapse. EMT-like CLL exhibit high genomic stability, reduced benefit from the addition of rituximab and EMT-like differentiation is inhibited by induction of DNA damage. This work extends the perspective on CLL biology and risk categories in TP53 wild-type CLL. Furthermore, molecular targets identified within each subgroup provide opportunities for new treatment approaches. Chronic lymphocytic leukemia has been studied using multiple levels of omics data. Here, the authors use exome sequencing, SNP, protein and gene expression data to identify distinct biologic tumor subtypes with heterogeneous prognostic impact after chemo- or immunochemotherapy. [ABSTRACT FROM AUTHOR]
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Titel: |
Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.
|
---|---|
Autor/in / Beteiligte Person: | Bloehdorn, Johannes ; Braun, Andrejs ; Taylor-Weiner, Amaro ; Jebaraj, Billy Michael Chelliah ; Robrecht, Sandra ; Krzykalla, Julia ; Pan, Heng ; Giza, Adam ; Akylzhanova, Gulnara ; Holzmann, Karlheinz ; Scheffold, Annika ; Johnston, Harvey E. ; Yeh, Ru-Fang ; Klymenko, Tetyana ; Tausch, Eugen ; Eichhorst, Barbara ; Bullinger, Lars ; Fischer, Kirsten ; Weisser, Martin ; Robak, Tadeusz |
Zeitschrift: | Nature Communications, Jg. 12 (2021-09-13), Heft 1, S. 1-18 |
Veröffentlichung: | 2021 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (print) |
DOI: | 10.1038/s41467-021-25403-y |
Schlagwort: |
|
Sonstiges: |
|