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| 001 | 172528 | ||
| 005 | 20240229133720.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-021-25403-y |2 doi |
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| 041 | _ | _ | |a English |
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| 100 | 1 | _ | |a Bloehdorn, Johannes |0 0000-0003-1433-9702 |b 0 |
| 245 | _ | _ | |a Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia. |
| 260 | _ | _ | |a [London] |c 2021 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a #LA:B061# |
| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Braun, Andrejs |0 0000-0003-0925-5598 |b 1 |
| 700 | 1 | _ | |a Taylor-Weiner, Amaro |b 2 |
| 700 | 1 | _ | |a Jebaraj, Billy Michael Chelliah |b 3 |
| 700 | 1 | _ | |a Robrecht, Sandra |b 4 |
| 700 | 1 | _ | |a Krzykalla, Julia |0 P:(DE-He78)5a7a75d1b29b770f98f1bb2062fc3df9 |b 5 |u dkfz |
| 700 | 1 | _ | |a Pan, Heng |b 6 |
| 700 | 1 | _ | |a Giza, Adam |b 7 |
| 700 | 1 | _ | |a Akylzhanova, Gulnara |b 8 |
| 700 | 1 | _ | |a Holzmann, Karlheinz |b 9 |
| 700 | 1 | _ | |a Scheffold, Annika |b 10 |
| 700 | 1 | _ | |a Johnston, Harvey E |b 11 |
| 700 | 1 | _ | |a Yeh, Ru-Fang |b 12 |
| 700 | 1 | _ | |a Klymenko, Tetyana |b 13 |
| 700 | 1 | _ | |a Tausch, Eugen |b 14 |
| 700 | 1 | _ | |a Eichhorst, Barbara |b 15 |
| 700 | 1 | _ | |a Bullinger, Lars |b 16 |
| 700 | 1 | _ | |a Fischer, Kirsten |b 17 |
| 700 | 1 | _ | |a Weisser, Martin |b 18 |
| 700 | 1 | _ | |a Robak, Tadeusz |0 0000-0002-3411-6357 |b 19 |
| 700 | 1 | _ | |a Schneider, Christof |b 20 |
| 700 | 1 | _ | |a Gribben, John |0 0000-0002-8505-7430 |b 21 |
| 700 | 1 | _ | |a Dahal, Lekh N |0 0000-0001-8390-6593 |b 22 |
| 700 | 1 | _ | |a Carter, Mathew J |b 23 |
| 700 | 1 | _ | |a Elemento, Olivier |0 0000-0002-8061-9617 |b 24 |
| 700 | 1 | _ | |a Landau, Dan A |0 0000-0003-2346-9541 |b 25 |
| 700 | 1 | _ | |a Neuberg, Donna S |0 0000-0003-2566-3145 |b 26 |
| 700 | 1 | _ | |a Cragg, Mark S |b 27 |
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| 700 | 1 | _ | |a Hallek, Michael |b 29 |
| 700 | 1 | _ | |a Wu, Catherine J |0 0000-0002-3348-5054 |b 30 |
| 700 | 1 | _ | |a Döhner, Hartmut |b 31 |
| 700 | 1 | _ | |a Stilgenbauer, Stephan |b 32 |
| 700 | 1 | _ | |a Mertens, Daniel |0 P:(DE-He78)833c06a995d272b78f3a20df3eba6e9e |b 33 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1038/s41467-021-25403-y |g Vol. 12, no. 1, p. 5395 |0 PERI:(DE-600)2553671-0 |n 1 |p 5395 |t Nature Communications |v 12 |y 2021 |x 2041-1723 |
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