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T. Yokokawa et al.
atherosclerosis. However, given that our data from murine studies and clinical observations strongly indicate that hematopoietic JAK2 V617F plays crucial roles in the development of AA, we propose that JAK2 V617F-posi- tive clonal hematopoiesis may be also involved in the
formation and progression of AA regardless of the hema- tological phenotypes of MPN.57
The limitation of the present study is the small number of patients with MPN included while thrombosis and non-thrombosis categories were also small subsets for
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Figure 7. Ruxolitinib attenuates the formation of abdominal aortic aneurysms induced by hematopoietic JAK2 V617F. (A) Schematic diagram of the experimental design. The ApoE-/- recipients transplanted with JAK2V617F bone marrow cells (JAK2V617F-BMT) were administered with vehicle (0.5% methylcellulose) or ruxolitinib was orally at 60 mg/kg twice daily for 4 weeks along with continuous angiotensin II ( Ang II, 1900 ng/kg per min) infusion. (B) Blood cell counts at 4 weeks (n=6 each) and (C) systolic blood pressure (BP) at baseline (n=9–10), 2 weeks (n=9–10), and 4 weeks (n=9–10) in the vehicle- or ruxolitinib-treated JAK2V617F-BMT mice. (D) Abdominal aorta diameter at the baseline (n=11 each), 2 weeks (n=11 each), and 4 weeks (n=11 each). (E) Representative images from the aorta. Scale bars, 5 mm. (F) Abdominal aortic aneurysm (AAA)-free survival rate in the vehicle- or ruxolitinib-treated JAK2V617F-BMT mice (n=11 each) by log-rank test. (G) A typical image of gelatin zymography using homogenates from abdominal aortas. All data are presented as mean ± standard error of the mean. *P<0.05 vs. the vehicle group by the unpaired Student’s t-test. WBC: white blood cell count; RBC: red blood cell count; Hb: hemoglobin concentration; Plt: platelet count; BP: blood pressure; MMP: matrix metalloproteinase.
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haematologica | 2021; 106(7)