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. 2017 Aug 11;32(2):462–469. doi: 10.1038/leu.2017.233

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Copyright © 2018 The Author(s)

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

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JAK2^V617F-bearing vascular niche contributes to JAK2^V617F clonal expansion in MPN. (a) Competitive marrow transplantation scheme. (b) Following the competitive transplantation experiment of both Tie2/FF1 marrow cells (CD45.2) and competitor wild-type marrow cells (CD45.1), Tie2/FF1 recipients displayed higher peripheral blood CD45.2 (that is, JAK2^V617F donor) chimerism than the WT control recipients. (c) By 18 weeks post transplantation, Tie2/FF1 recipients developed a MPN phenotype with significant neutrophilia and thrombocytosis. (d) Spleens collected from mice 18 weeks following transplantation showed moderate splenomegaly in the Tie2/FF1 recipients (black bar) compared with WT recipients (gray bar) (spleen weight 0.269 vs 0.148 g, P=0.073). (e) Tie2/FF1 recipients also exhibited significant increases in total hematopoietic colonies (1.8-fold, P=0.008), BFU-e (1.8-fold, P=0.026), and CFU-GM (1.7-fold, P=0.006) colonies compared with WT recipients. (f) CD45.2⁺CD150⁺CD48⁻ (JAK2^V617F-mutant) HSPCs were expanded in marrow of Tie2/FF1 recipients compared to WT recipients. In contrast, there was no difference in WT CD45.1⁺CD150⁺CD48⁻ cell numbers between the Tie2/FF1 recipients and controls. (g, h) Single colony analysis for JAK2^V617F-mutant (g) and JAK2^WT donor-derived (h) colonies in Tie2/FF1 recipients and WT recipients.