Author/Authors :
Mullally، نويسنده , , Ann E. Lane، نويسنده , , Steven W. and Ball، نويسنده , , Brian and Megerdichian، نويسنده , , Christine and Okabe، نويسنده , , Rachel and Al-Shahrour، نويسنده , , Fatima and Paktinat، نويسنده , , Mahnaz and Haydu، نويسنده , , J. Erika and Housman، نويسنده , , Elizabeth and Lord، نويسنده , , Allegra M. and Wernig، نويسنده , , Gerlinde and Kharas، نويسنده , , Michael G. and Mercher، نويسنده , , Thomas and Kutok، نويسنده , , Jeffery L. and Gilliland، نويسنده , , D. Gary and Ebert، نويسنده , , Benjamin L.، نويسنده ,
Abstract :
Summary
ort 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.
