Figure 1.
PF4iCre;JAK2V617F/WTmice develop a typical MPN with detection of JAK2V617F mutation in myeloid cells. (A) Blood cell counts of PF4-iCre;JAK2V617F/WT mice and littermate controls. Data are presented as mean ± standard deviation (n = 5-24 JAK2WT; n = 5-29 JAK2V617F). Statistical significance determined by 2-tailed unpaired t test. *P < .05; **P < .01; ***P < .001; (B) Spleen weight (also showing spleens collected) in 12-week-old PF4iCre;JAK2V617F/WT mice. Data are presented as individual values and mean ± standard error of the mean (n = 5 JAK2WT; n = 9 JAK2V617F). (C) Histologic examination of the spleen (HES coloration). (Top) Representative normal splenic architecture observed in 12-week-old PF4iCre;JAK2WT/WT mice. (Middle) Histological features observed in 12-week-old PF4iCre;JAK2V617F/WT mice with myeloid hyperplasia without disturbance of the white pulp. (Bottom) Histological features observed in 18-week-old PF4iCre;JAK2V617F/WT mice with myeloid hyperplasia associated with a near disappearance of the white pulp. (D) Bone marrow myeloid cells from 12-week-old were sorted based on the expression of CD42 (megakaryocytes), Gr-1 (Ly6G+C, granulocytes precursors), Ter119 (erythroid cells), or CD31 (endothelial cells); the JAK2V617F mutation was searched in these cell populations by allele-specific genotyping. The graph represents the wild-type allele relative quantity on the x-axis and the V617F allele relative quantity on the y-axis. Standard curves (0%, 12.5%, 25%, 50%) of V617F allele burden are indicated by circles. Samples are indicated by crosses. (E) The table details the results of allelic burdens observed for the different cell populations sorted in wild-type and mutated mice, as determined from the discrimination plot (D).