Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms.
Andrew J DunbarRobert L BowmanYoung C ParkKavi O'ConnorFranco IzzoRobert M MyersAbdul KarzaiZachary J ZaroogianWon Jun KimInes Fernandez-MaestreMichael R WaartsAbbas NazirWenbin XiaoTamara CodilupiMax BrodskyMirko FarinaLouise CaiSheng F CaiBenjamin WangWenbin AnJulie L YangShoron MowlaShira E EismanAmritha Varshini Hanasoge SomasundaraJacob Lowell GlassTanmay MishraRemie HoustonEmily GuzzardiAnthony R Martinez BenitezAaron D VinyRichard P KocheSara C MeyerDan A LandauRoss L LevinePublished in: Cancer discovery (2024)
Current JAK inhibitors to treat myeloproliferative neoplasms are ineffective at eradicating mutant cells. We developed an endogenously expressed Jak2V617F dual-recombinase knock-in/knock-out model to investigate Jak2V617F oncogenic reversion in vivo. Jak2V617F deletion abrogates MPN features and depletes disease-sustaining MPN stem cells, suggesting improved Jak2V617F targeting offers the potential for greater therapeutic efficacy. See related commentary by Celik and Challen, p. 701. This article is featured in Selected Articles from This Issue, p. 695.