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Series GSE44961 Query DataSets for GSE44961
Status Public on Mar 09, 2013
Title Depletion of Jak2V617F MPN-propagating stem cells by interferon-alpha in a murine model of polycythemia vera
Organism Mus musculus
Experiment type Expression profiling by array
Summary Interferon alpha (IFNa) is an effective treatment for patients with myeloproliferative neoplasms (MPN). In addition to inducing hematological responses in most MPN patients, IFNa reduces the JAK2V617F allelic burden and can render the JAK2V617F mutant clone undetectable in some patients. The precise mechanism underlying these responses is incompletely understood and whether the molecular responses that are seen occur due to the effects of IFNa on JAK2V617F mutant stem cells is debated. Using a murine model of Jak2V617F MPN, we investigated the effects of IFNa on Jak2V617F MPN-propagating stem cells in vivo. We report that IFNa treatment induces hematological responses in the model and causes depletion of Jak2V617F MPN-propagating cells over time, impairing disease transplantation. We demonstrate that IFNa treatment induces cell-cycle activation of Jak2V617F mutant long-term hematopoietic stem cells (LT-HSC) and promotes a predetermined erythroid-lineage differentiation program. These findings provide insights into the differential effects of IFNa on Jak2V617F mutant and normal hematopoiesis and suggest that IFNa achieves molecular remissions in MPN patients through its effects on MPN stem cells. Furthermore, these results support combinatorial therapeutic approaches in MPN, by concurrently depleting dormant JAK2V617F MPN-propagating stem cells with IFNa and targeting the proliferating downstream progeny with JAK2-inhibitors or cytotoxic chemotherapy.
 
Overall design HSC-enriched population from WT (CD45.1) or Jak2VF knockin (CD45.2), after 4 weeks of interferon alpha or vehicle treatment. N=4 per condition
 
Contributor(s) Mullally A, Bruedigam C, Poveromo LP, Heidel FH, Purdon A, Vu T, Austin R, Heckl D, Breyfogle LJ, Paine Kuhn C, Kalaitzidis D, Armstrong SA, Williams DA, Hill GR, Ebert BL, Lane SW
Citation(s) 23487027
Submission date Mar 07, 2013
Last update date Jun 14, 2018
Contact name Steven Lane
Organization name QIMR
Street address 300 Herston Rd
City Brisbane
ZIP/Postal code 4064
Country Australia
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (16)
GSM1094492 WT vehicle (7991003028_A)
GSM1094493 Jak2VF vehicle (7991003028_B)
GSM1094494 WT Interferon (7991003028_C)
Relations
BioProject PRJNA192679

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE44961_RAW.tar 3.1 Mb (http)(custom) TAR
GSE44961_non-normalized.txt.gz 2.6 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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