Skip to main content

β-Arrestin2 mediates progression of murine primary myelofibrosis.

Publication ,  Journal Article
Rein, LA; Wisler, JW; Kim, J; Theriot, B; Huang, L; Price, T; Yang, H; Chen, M; Chen, W; Sipkins, D; Fedoriw, Y; Walker, JK; Premont, RT ...
Published in: JCI Insight
December 21, 2017

Primary myelofibrosis is a myeloproliferative neoplasm associated with significant morbidity and mortality, for which effective therapies are lacking. β-Arrestins are multifunctional adaptor proteins involved in developmental signaling pathways. One isoform, β-arrestin2 (βarr2), has been implicated in initiation and progression of chronic myeloid leukemia, another myeloproliferative neoplasm closely related to primary myelofibrosis. Accordingly, we investigated the relationship between βarr2 and primary myelofibrosis. In a murine model of MPLW515L-mutant primary myelofibrosis, mice transplanted with donor βarr2-knockout (βarr2-/-) hematopoietic stem cells infected with MPL-mutant retrovirus did not develop myelofibrosis, whereas controls uniformly succumbed to disease. Although transplanted βarr2-/- cells homed properly to marrow, they did not repopulate long-term due to increased apoptosis and decreased self-renewal of βarr2-/- cells. In order to assess the effect of acute loss of βarr2 in established primary myelofibrosis in vivo, we utilized a tamoxifen-induced Cre-conditional βarr2-knockout mouse. Mice that received Cre (+) donor cells and developed myelofibrosis had significantly improved survival compared with controls. These data indicate that lack of antiapoptotic βarr2 mediates marrow failure of murine hematopoietic stem cells overexpressing MPLW515L. They also indicate that βarr2 is necessary for progression of primary myelofibrosis, suggesting that it may serve as a novel therapeutic target in this disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

December 21, 2017

Volume

2

Issue

24

Location

United States

Related Subject Headings

  • beta-Arrestin 2
  • Tamoxifen
  • Primary Myelofibrosis
  • Mice, Knockout
  • Male
  • Hematopoietic Stem Cells
  • Hematopoietic Stem Cell Transplantation
  • Graft Survival
  • Disease Progression
  • Disease Models, Animal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rein, L. A., Wisler, J. W., Kim, J., Theriot, B., Huang, L., Price, T., … Lefkowitz, R. J. (2017). β-Arrestin2 mediates progression of murine primary myelofibrosis. JCI Insight, 2(24). https://doi.org/10.1172/jci.insight.98094
Rein, Lindsay Am, James W. Wisler, Jihee Kim, Barbara Theriot, LiYin Huang, Trevor Price, Haeyoon Yang, et al. “β-Arrestin2 mediates progression of murine primary myelofibrosis.JCI Insight 2, no. 24 (December 21, 2017). https://doi.org/10.1172/jci.insight.98094.
Rein LA, Wisler JW, Kim J, Theriot B, Huang L, Price T, et al. β-Arrestin2 mediates progression of murine primary myelofibrosis. JCI Insight. 2017 Dec 21;2(24).
Rein, Lindsay Am, et al. “β-Arrestin2 mediates progression of murine primary myelofibrosis.JCI Insight, vol. 2, no. 24, Dec. 2017. Pubmed, doi:10.1172/jci.insight.98094.
Rein LA, Wisler JW, Kim J, Theriot B, Huang L, Price T, Yang H, Chen M, Chen W, Sipkins D, Fedoriw Y, Walker JK, Premont RT, Lefkowitz RJ. β-Arrestin2 mediates progression of murine primary myelofibrosis. JCI Insight. 2017 Dec 21;2(24).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

December 21, 2017

Volume

2

Issue

24

Location

United States

Related Subject Headings

  • beta-Arrestin 2
  • Tamoxifen
  • Primary Myelofibrosis
  • Mice, Knockout
  • Male
  • Hematopoietic Stem Cells
  • Hematopoietic Stem Cell Transplantation
  • Graft Survival
  • Disease Progression
  • Disease Models, Animal