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Acute lymphoblastic leukemia (ALL)

B cell lymphoma 2
(BCL-2; BCL2); tyrosine kinase 2
(TYK2); signal transducer and activator of transcription 1 (STAT1)

Mouse and cell culture studies suggest inhibiting the TYK2-STAT1-BCL2 signaling pathway could help treat T cell ALL. In mice grafted with leukemic cells from patients with T cell ALL, small interfering RNA against TYK2 in the grafted cells decreased leukemic cell viability compared with control siRNA in five of eight cases. A series of cell culture studies identified STAT1 and BCL2 as downstream mediators of TYK2. In 19 T cell ALL cell lines, pharmacological blockade of TYK2 with pan-Janus kinase inhibitors reduced ALL cell viability. Next steps could include evaluating pharmacological TYK2 inhibitors in animal models of ALL.
Sareum Holdings plc has a TYK2 inhibitor in preclinical development to treat autoimmune diseases.

SciBX 6(12); doi:10.1038/scibx.2013.281
Published online March 28, 2013

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Sanda, T. et al. Cancer Discov.; published online March 7, 2013;
Contact: A. Thomas Look, Dana-Farber Cancer Institute, Boston, Mass.