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Blood, Vol. 107, Issue 11, 4274-4281, June 1, 2006
Expression of Jak2V617F causes a polycythemia vera–like disease with associated myelofibrosis in a murine bone marrow transplant model
Blood Wernig et al.
107: 4274
Supplemental materials for: Wernig et al
Files in this Data Supplement:
- Figure S1 (A-L): Jak2V617F and Jak2wt bone marrow transplant model histopathology in C57Bl/6 mice (JPG, 168 KB)
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Histology of Jak2V617F and Jak2wt transduced C57Bl/6 mice showing pathology in representative sections of peripheral blood (PB; A-B), bone marrow (BM; C-D), spleen (E-H), and liver (I-L). Peripheral blood smear of a representative C57Bl/6 Jak2V617F transduced animal (A, 600×; Wright-Giemsa) exhibits increased numbers of reticulocytes compared with a C57Bl/6 Jak2wt animal (B, 600×; Wright-Giemsa), but no significant differences in leukocyte numbers or differential. BM images from Jak2wt animals display preserved marrow architecture with normal ratios of myeloid to erythroid elements and unremarkable megakaryocytes (D, 600×, H&E). Comparatively, BM sections from Jak2V617F mutant animals demonstrate marrow elements comprised of a prominent population of maturing myeloid cells with mildly to moderately increased numbers of megakaryocytes including large, atypical forms occurring in occasional clusters (C; 600×, H&E) and showing emperipolesis of neutrophils in megakaryocyte cytoplasm (arrows). Spleen sections from Jak2V617F mice display a marked expansion of red pulp (E; 40x, H&E) compared with Jak2wt spleens (F; 40×, H&E) that is predominantly comprised of maturing erythroid elements, and only occasional megakaryocytic and mature myeloid forms (G; 600×, H&E) compared with spleens from Jak2wt transplanted animals (F & H, 40× & 600×, H&E). Liver images from Jak2V617F mice illustrate focal evidence of extramedullary hematopoiesis with occasional megakaryocytes (I & K; 100x & 600×, H&E), but notably absent in livers from Jak2wt animals (J & L; 100× & 600×, H&E).
- Figure S2: Flow analysis of BM and spleen comparing Jak2V617F and Jak2wt in C57Bl/6 (JPG, 149 KB)
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Erythroid cells positive for ter119 are ∼five-fold increased in spleen of Jak2V617F compared to Jak2wt and most of them are double positive for ter119/CD71. In BM of Jak2V617F there is a ∼1.4-fold increase in cells double positive for Gr1/Mac1 compared to Jak2wt but at a high normal range and ∼3.6-fold increase in spleens of Jak2V617F compared to spleens of Jak2wt. B220 positive B cells were proportionately decreased in spleen of Jak2V617F compared to Jak2wt (One representative experiment out of 10).
- Figure S3: Comparison of hematocrit levels in Balb/C and C57Bl/6 mice expressing Jak2V617F or Jak2wt over time (JPG, 66.8 KB)
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Hcts were assessed at different time points from 3 weeks to 12 weeks. In Jak2V617F expressing Balb/C (A) and C57Bl/6 (B) mice stably elevated hcts were detectable which were at normal levels in mice expressing Jak2wt.
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