TY  - JOUR
AU  - Bloehdorn, Johannes
AU  - Braun, Andrejs
AU  - Taylor-Weiner, Amaro
AU  - Jebaraj, Billy Michael Chelliah
AU  - Robrecht, Sandra
AU  - Krzykalla, Julia
AU  - Pan, Heng
AU  - Giza, Adam
AU  - Akylzhanova, Gulnara
AU  - Holzmann, Karlheinz
AU  - Scheffold, Annika
AU  - Johnston, Harvey E
AU  - Yeh, Ru-Fang
AU  - Klymenko, Tetyana
AU  - Tausch, Eugen
AU  - Eichhorst, Barbara
AU  - Bullinger, Lars
AU  - Fischer, Kirsten
AU  - Weisser, Martin
AU  - Robak, Tadeusz
AU  - Schneider, Christof
AU  - Gribben, John
AU  - Dahal, Lekh N
AU  - Carter, Mathew J
AU  - Elemento, Olivier
AU  - Landau, Dan A
AU  - Neuberg, Donna S
AU  - Cragg, Mark S
AU  - Benner, Axel
AU  - Hallek, Michael
AU  - Wu, Catherine J
AU  - Döhner, Hartmut
AU  - Stilgenbauer, Stephan
AU  - Mertens, Daniel
TI  - Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.
JO  - Nature Communications
VL  - 12
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2021-02076
SP  - 5395
PY  - 2021
N1  - #LA:B061#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34518531
C2  - pmc:PMC8438057
DO  - DOI:10.1038/s41467-021-25403-y
UR  - https://inrepo02.dkfz.de/record/172528
ER  -