@article{ad99c746ee5b488b8bed18a480db1e0d,
title = "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.",
keywords = "CELLCYCLE",
author = "Ann Mullally and Lane, {Steven W.} and Brian Ball and Christine Megerdichian and Rachel Okabe and Fatima Al-Shahrour and Mahnaz Paktinat and Haydu, {J. Erika} and Elizabeth Housman and Lord, {Allegra M.} and Gerlinde Wernig and Kharas, {Michael G.} and Thomas Mercher and Kutok, {Jeffery L.} and Gilliland, {D. Gary} and Ebert, {Benjamin L.}",
note = "Funding Information: We gratefully acknowledge transgenic core facilities supported by NIH P30 DK49216, NIDDK Centers of Excellence in Hematology for generating chimeric mice, and TargeGen Inc. (San Diego, CA, USA) for supplying TG101348. We warmly thank Drs. Ross Levine and Demetrios Kalaitzidis for critically reviewing the manuscript and all members of the Gilliland and Ebert laboratories for their insights and collegiality. This work was supported with funding from the Myeloproliferative Disorders Foundation (Chicago, IL), R01 HL082950 (NIH/NHLBI), and P01 CA 66996-11 (NIH/NCI). A.M. has received T32HL0763 funding (NIH/NHLBI) and support from the Jeanne D. Housman Fund for Research on Myeloproliferative Disorders and is a 2010 ASH Scholar recipient. Authorship contributions are as follows. A.M., S.W.L., D.G.G., and B.L.E. designed experiments. A.M., S.W.L., B.B., C.M., R.O., and F.A.-S. performed experiments and analyzed data. A.M. wrote the manuscript with assistance from S.W.L. All authors provided critical review of the manuscript. Conflict-of-interest disclosure: B.L.E. has received research support from GlaxoSmithKline. D.G.G. is now an employee of Merck. ",
year = "2010",
month = jun,
day = "15",
doi = "10.1016/j.ccr.2010.05.015",
language = "English",
volume = "17",
pages = "584--596",
journal = "Cancer Cell",
issn = "1535-6108",
number = "6",
}