Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells.

Abstract

We report a Jak2V617F knockin mouse myeloproliferative neoplasm (MPN) model resembling human polycythemia vera (PV). The MPN is serially transplantable and we demonstrate that the hematopoietic stem cell (HSC) compartment has the unique capacity for disease initiation but does not have a significant selective competitive advantage over wild-type HSCs. In contrast, myeloid progenitor populations are expanded and skewed toward the erythroid lineage, but cannot transplant the disease. Treatment with a JAK2 kinase inhibitor ameliorated the MPN phenotype, but did not eliminate the disease-initiating population. These findings provide insights into the consequences of JAK2 activation on HSC differentiation and function and have the potential to inform therapeutic approaches to JAK2V617F-positive MPN.

DOI: 10.1016/j.ccr.2010.05.015
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@article{Mullally2010PhysiologicalJE, title={Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells.}, author={Ann Mullally and Steven W Lane and Brian Ball and Christine Megerdichian and Rachel O. Okabe and F{\'a}tima Al-Shahrour and Mahnaz Paktinat and Jeffrey Haydu and Elizabeth Housman and Allegra M. Lord and Gerlinde Wernig and Michael G Kharas and Thomas Mercher and Jeffery L. Kutok and Dwight Gary Gilliland and Benjamin L. Ebert}, journal={Cancer cell}, year={2010}, volume={17 6}, pages={584-96} }