Authors
Helena Sorger, Saptaswa Dey, Pablo Augusto Vieyra‐Garcia, Daniel Pölöske, Andrea R Teufelberger, Elvin D de Araujo, Abootaleb Sedighi, Ricarda Graf, Benjamin Spiegl, Isaac Lazzeri, Till Braun, Ines Garces de los Fayos Alonso, Michaela Schlederer, Gerald Timelthaler, Petra Kodajova, Christine Pirker, Marta Surbek, Michael Machtinger, Thomas Graier, Isabella Perchthaler, Yi Pan, Regina Fink‐Puches, Lorenzo Cerroni, Jennifer Ober, Moritz Otte, Jana D Albrecht, Gary Tin, Ayah Abdeldayem, Pimyupa Manaswiyoungkul, Olasunkanmi O Olaoye, Martin L Metzelder, Anna Orlova, Walter Berger, Marion Wobser, Jan P Nicolay, Fiona André, Van Anh Nguyen, Heidi A Neubauer, Roman Fleck, Olaf Merkel, Marco Herling, Ellen Heitzer, Patrick T Gunning, Lukas Kenner, Richard Moriggl, Peter Wolf
Publication date
2022/12/7
Journal
EMBO Molecular Medicine
Volume
14
Issue
12
Pages
e15200
Description
Leukemic cutaneous T‐cell lymphomas (L‐CTCL) are lymphoproliferative disorders of skin‐homing mature T‐cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L‐CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L‐CTCL, which correlated with the increased clonal T‐cell count in the blood. Dual inhibition of STAT3/5 using small‐molecule degraders and multi‐kinase blockers abolished L‐CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L‐CTCL …
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Scholar articles
H Sorger, S Dey, PA Vieyra‐Garcia, D Pölöske… - EMBO Molecular Medicine, 2022