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

Mullally, Ann, Lane, Steven W., Ball, Brian, Megerdichian, Christine, Okabe, Rachel, Al-Shahrour, Fatima, Paktinat, Mahnaz, Haydu, J. Erika, Housman, Elizabeth, Lord, Allegra M., Wernig, Gerlinde, Kharas, Michael G., Mercher, Thomas, Kutok, Jeffery L., Gilliland, D. Gary and Ebert, Benjamin L. (2010) Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietis stem and progenitor cells. CANCER CELL, 17 6: 584-596. doi:10.1016/j.ccr.2010.05.015


Author Mullally, Ann
Lane, Steven W.
Ball, Brian
Megerdichian, Christine
Okabe, Rachel
Al-Shahrour, Fatima
Paktinat, Mahnaz
Haydu, J. Erika
Housman, Elizabeth
Lord, Allegra M.
Wernig, Gerlinde
Kharas, Michael G.
Mercher, Thomas
Kutok, Jeffery L.
Gilliland, D. Gary
Ebert, Benjamin L.
Title Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietis stem and progenitor cells
Formatted title
Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietis stem and progenitor cells
Journal name CANCER CELL   Check publisher's open access policy
ISSN 1535-6108
1878-3686
Publication date 2010-06
Sub-type Article (original research)
DOI 10.1016/j.ccr.2010.05.015
Volume 17
Issue 6
Start page 584
End page 596
Total pages 13
Place of publication Cambridge, United States
Publisher Cell Press
Collection year 2011
Language eng
Formatted 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. © 2010 Elsevier Inc.
Keyword Chronic myelomonocytic leukemia
Chronic myeloid-leukaemia
Tyrosine kinase Jak2
Vera-like disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Sun, 04 Jul 2010, 00:06:31 EST