HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Interferon-alpha targets JAK2V617F-positive hematopoietic progenitor cells and acts through the p38 MAPK pathway.

AbstractOBJECTIVE:
Interferon-alpha (IFNalpha) therapy leads to hematological remissions and a reduction of the JAK2V617F allele burden in patients with polycythemia vera (PV). In this study, the cellular target by which IFNalpha affects hematopoiesis in PV patients was evaluated.
MATERIALS AND METHODS:
CD34(+) cells were isolated from normal bone marrow and the peripheral blood of patients with PV and were treated in vitro with each of the three commercially available forms of IFNalpha: IFNalpha 2b, pegylated IFNalpha 2a (Peg-IFNalpha 2a), and pegylated IFNalpha 2b (Peg-IFNalpha 2b).
RESULTS:
Each form of IFNalpha was equally potent in suppressing hematopoietic colony formation by normal CD34(+) cells, but Peg-IFNalpha 2a and IFNalpha 2b were more effective than Peg-IFNalpha 2b in inhibiting burst-forming unit erythroid-derived colony formation by PV CD34(+) cells. In addition, exposure of PV CD34(+) cells to equal doses of Peg-IFNalpha 2a and IFNalpha 2b resulted in a 38% to 40% reduction in the proportion of JAK2V617F-positive hematopoietic progenitor cells (HPC), while equivalent doses of Peg-IFNalpha 2b did not reduce the number of malignant HPC. Further studies explored the mechanism by which IFNalpha induced PV HPC growth inhibition. Treatment of Peg-IFNalpha 2a increased the rate of apoptosis of PV CD34(+) cells and the phosphorylation/activation of p38 mitogen-activated protein kinase in PV CD34(+) cells, while the p38-specific inhibitor SB203580 reversed the growth inhibition and apoptosis induced by Peg-IFNalpha 2a.
CONCLUSION:
These data suggest that low doses of IFNalpha selectively and directly suppress PV JAK2V617F HPC and that these agents act through the p38 mitogen-activated protein kinase pathway.
AuthorsMin Lu, Wei Zhang, Yan Li, Dmitriy Berenzon, Xiaoli Wang, Jiapeng Wang, John Mascarenhas, Mingjiang Xu, Ronald Hoffman
JournalExperimental hematology (Exp Hematol) Vol. 38 Issue 6 Pg. 472-80 (Jun 2010) ISSN: 1873-2399 [Electronic] Netherlands
PMID20303384 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antigens, CD34
  • Interferon-alpha
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Antigens, CD34 (immunology)
  • Blotting, Western
  • Flow Cytometry
  • Hematopoiesis
  • Hematopoietic Stem Cells (drug effects, enzymology, immunology)
  • Humans
  • Interferon-alpha (pharmacology)
  • Polymerase Chain Reaction
  • p38 Mitogen-Activated Protein Kinases (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: