Selective dependency of CALR-mutant myeloproliferative neoplasms on TYK2 signaling (Leukemia, Nature) - Sep 24, 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....In primary samples, deucravacitinib significantly suppressed colony growth in ET and PMF but not PV, and selectively reduced CALR- but not JAK2V617F-mutant allele burden. Similarly, CALR-mutant patient-specific iPSC-derived CD34+ progenitors showed increased TYK2 phosphorylation and were more sensitive to TYK2 inhibition than their JAK2V617F counterparts."
CALR • JAK2V617F • Preclinical • Essential Thrombocythemia • Myeloproliferative Neoplasm • Polycythemia Vera
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