Selective dependency of CALR-mutant myeloproliferative neoplasms on TYK2 signaling. (PubMed, Leukemia) - Sep 25, 2026 - "The TYK2 inhibitor deucravacitinib reduced viability and STAT3/5 phosphorylation in CALRdel52/ins5- and MPLW515K- but not JAK2V617F-mutant cells, with enhanced efficacy when combined with the JAK2-selective inhibitor fedratinib. Similarly, CALR-mutant patient-specific iPSC-derived CD34+ progenitors showed increased TYK2 phosphorylation and were more sensitive to TYK2 inhibition than their JAK2V617F counterparts. These findings identify TYK2 as a selective vulnerability in CALR-mutant MPN and support combined TYK2/JAK2 inhibition strategies to overcome JAK2-dependent resistance."
CALR • JAK2V617F • Journal • Myeloproliferative Neoplasm • Oncology • CALR • CD34 • HSP90AA1 • MPL • TYK2
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Alessia Piergentili; Angela Galauner; Anna Spitzer; Bärbel Junge; Chiara Wirths; Christian Pecquet; Chunxiao Zhou; Giulia Rossetti; Jacob Piehler; Joelle Schifflers; Jonas Goßen; Kim Kricheldorf; Kristina Pannen; Laura Schulz; Marcelo A S de Toledo; Mia Mönnig; Milena Kalmer; Nicolas Chatain; Rebecca Lemanzyk; Siddharth Gupta; Stefan N Constantinescu; Stefan Tillmann; Steffen Koschmieder
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