Journal Article

DKFZ-2021-02076

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.

Bloehdorn, J. ; Braun, A. ; Taylor-Weiner, A. ; Jebaraj, B. M. C. ; Robrecht, S. ; Krzykalla, J.DKFZ* ; Pan, H. ; Giza, A. ; Akylzhanova, G. ; Holzmann, K. ; Scheffold, A. ; Johnston, H. E. ; Yeh, R.-F. ; Klymenko, T. ; Tausch, E. ; Eichhorst, B. ; Bullinger, L. ; Fischer, K. ; Weisser, M. ; Robak, T. ; Schneider, C. ; Gribben, J. ; Dahal, L. N. ; Carter, M. J. ; Elemento, O. ; Landau, D. A. ; Neuberg, D. S. ; Cragg, M. S. ; Benner, A.DKFZ* ; Hallek, M. ; Wu, C. J. ; Döhner, H. ; Stilgenbauer, S. ; Mertens, D. (Last author)DKFZ*

2021
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-021-25403-y

Abstract: 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.

Note: #LA:B061#

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Contributing Institute(s):

1. C060 Biostatistik (C060)
2. B061 Mechanismen der Leukämogenese (B061)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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