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000172528 1001_ $$00000-0003-1433-9702$$aBloehdorn, Johannes$$b0
000172528 245__ $$aMulti-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.
000172528 260__ $$a[London]$$bNature Publishing Group UK$$c2021
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000172528 520__ $$aKnowledge 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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000172528 7001_ $$00000-0003-0925-5598$$aBraun, Andrejs$$b1
000172528 7001_ $$aTaylor-Weiner, Amaro$$b2
000172528 7001_ $$aJebaraj, Billy Michael Chelliah$$b3
000172528 7001_ $$aRobrecht, Sandra$$b4
000172528 7001_ $$0P:(DE-He78)5a7a75d1b29b770f98f1bb2062fc3df9$$aKrzykalla, Julia$$b5$$udkfz
000172528 7001_ $$aPan, Heng$$b6
000172528 7001_ $$aGiza, Adam$$b7
000172528 7001_ $$aAkylzhanova, Gulnara$$b8
000172528 7001_ $$aHolzmann, Karlheinz$$b9
000172528 7001_ $$aScheffold, Annika$$b10
000172528 7001_ $$aJohnston, Harvey E$$b11
000172528 7001_ $$aYeh, Ru-Fang$$b12
000172528 7001_ $$aKlymenko, Tetyana$$b13
000172528 7001_ $$aTausch, Eugen$$b14
000172528 7001_ $$aEichhorst, Barbara$$b15
000172528 7001_ $$aBullinger, Lars$$b16
000172528 7001_ $$aFischer, Kirsten$$b17
000172528 7001_ $$aWeisser, Martin$$b18
000172528 7001_ $$00000-0002-3411-6357$$aRobak, Tadeusz$$b19
000172528 7001_ $$aSchneider, Christof$$b20
000172528 7001_ $$00000-0002-8505-7430$$aGribben, John$$b21
000172528 7001_ $$00000-0001-8390-6593$$aDahal, Lekh N$$b22
000172528 7001_ $$aCarter, Mathew J$$b23
000172528 7001_ $$00000-0002-8061-9617$$aElemento, Olivier$$b24
000172528 7001_ $$00000-0003-2346-9541$$aLandau, Dan A$$b25
000172528 7001_ $$00000-0003-2566-3145$$aNeuberg, Donna S$$b26
000172528 7001_ $$aCragg, Mark S$$b27
000172528 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b28$$udkfz
000172528 7001_ $$aHallek, Michael$$b29
000172528 7001_ $$00000-0002-3348-5054$$aWu, Catherine J$$b30
000172528 7001_ $$aDöhner, Hartmut$$b31
000172528 7001_ $$aStilgenbauer, Stephan$$b32
000172528 7001_ $$0P:(DE-He78)833c06a995d272b78f3a20df3eba6e9e$$aMertens, Daniel$$b33$$eLast author$$udkfz
000172528 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-021-25403-y$$gVol. 12, no. 1, p. 5395$$n1$$p5395$$tNature Communications$$v12$$x2041-1723$$y2021
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