The spleen is necessary for PV development through amplification of the
JAK2V617F erythroid compartment. A, Kinetics of spleen
weight (left) and pictures of spleens 3 weeks after transplantation of WT and
JAK2V617F BM cells (right). B, Kinetics of WT or
JAK2V617F cells contribution to the LSK compartment. C,
Kinetics of WT or JAK2V617F cells contribution to the
megakaryocyte–erythroid progenitors (MEP) and the CD71+Ter119+
erythroid compartments in the spleen. D, Percentage of
JAK2V617F LSK bar-coded clones shared between the irradiated leg, the
nonirradiated leg, and the spleen. E, Venn diagrams of bar-coded
CD71+Ter119+ erythroid (left top) and
CD11b+Gr1+ myeloid clones (right top) in the nonirradiated leg
and in the spleen and histograms showing the ratio of distribution of bar-coded
erythroid (left bottom) and myeloid (right bottom) clones in the nonirradiated leg
(NIR E, NIR M) and in the spleen (spleen E, spleen M; n = 3).
F, Experimental design (top) and survival curve (bottom) of mice after
splenectomy one week after transplantation of JAK2V617F or WT BM cells in a
single irradiated leg. G, Kinetics of blood parameters in mice after
splenectomy 1 week after transplantation of JAK2V617F or WT BM cells in a
single irradiated leg. H, Kinetics of blood cell chimerism in mice after
splenectomy one week after transplantation of JAK2V617F or WT BM cells in a
single irradiated leg. I, JAK2V617F, WT and endogenous cells
contributions to the irradiated and nonirradiated legs to the
CD11b+Gr1+ myeloid and the CD71+Ter119+
erythroid compartments. J, JAK2V617F, WT and endogenous cells
contributions to the irradiated and nonirradiated legs to the LT-HSC compartment 26
weeks after transplantation. K, Total hematopoietic cell number in the
irradiated and nonirradiated legs 26 weeks after transplantation. Data are mean ±SEM
from 8 to 12 mice. Significance was assessed using unpaired two-tailed
t test and two-way ANOVA followed by post hoc
analysis (*, P < 0.05; **, P < 0.01; ***,
P < 0.001; ****, P < 0.0001; B
and C, asterisks denote chimerism, and # denotes percentage of
cells).