Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia

We evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against Janus kinases. Solving the structure of FDA-approved type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 JH1 tyrosine kinase domain enabled the rational design and optimization of Cereblon (CRBN)-directed JAK PROTACs utilizing multiple derivatives of JAK inhibitors, linkers and CRBN-specific molecular glues. The resulting JAK PROTACs were evaluated for target degradation by proteomic approaches, and activity tested in CRLF2-rearranged cell line and xenograft models of ALL.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001007569	RNAseq data set, Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia	Illumina NovaSeq 6000	11
EGAD00001007570	WGS data set of 11 xenograft samples, Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia	Illumina NovaSeq 6000	11

Publications	Citations
Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia. Chang Y, Min J, Jarusiewicz JA, Actis M, Yu-Chen Bradford S, Mayasundari A, Yang L, Chepyala D, Alcock LJ, Roberts KG, Nithianantham S, Maxwell D, Rowland L, Larsen R, Seth A, Goto H, Imamura T, Akahane K, Hansen BS, Pruett-Miller SM, Paietta EM, Litzow MR, Qu C, Yang JJ, Fischer M, Rankovic Z, Mullighan CG. Blood 138: 2021 2313-2326	27

Publications

Citations

Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia.
Chang Y, Min J, Jarusiewicz JA, Actis M, Yu-Chen Bradford S, Mayasundari A, Yang L, Chepyala D, Alcock LJ, Roberts KG, Nithianantham S, Maxwell D, Rowland L, Larsen R, Seth A, Goto H, Imamura T, Akahane K, Hansen BS, Pruett-Miller SM, Paietta EM, Litzow MR, Qu C, Yang JJ, Fischer M, Rankovic Z, Mullighan CG. Blood 138: 2021 2313-2326