Fig. 1: Genetic targeting of ERK1/2 mitigates the MPN phenotype and impairs the Jak2V617F clone.

Jak2V617F CD45.2 bone marrow (BM) with intact (gray) or deficient (blue) ERK1/2 was transplanted in 1:1 ratio with Jak2WT CD45.1 BM into CD45.1 C57BL/6 recipient mice (for schema see Supplementary Fig. 3A). A Erythrocytosis reflected by increased hematocrit and reticulocytes was moderated by ERK1/2 deficiency in Jak2V617F settings (n = 10–11/group, shaded areas represent normal range). B CD45.2/CD45 chimerism reflecting Jak2V617F allele burden was significantly reduced by ERK1/2 deficiency in peripheral blood (n = 10–11/group) and BM 16 weeks after transplantation (n = 4–5/group). C BM fibrosis assessed by reticulin (Gömöri) staining 30 weeks after transplantation was not evident in ERK1/2 deficient Jak2V617F mice, whereas fibrosis was detected in Jak2V617F mice with intact ERK1/2 as reflected by fibrosis grading by a specialized hematopathologist blinded for the respective genotypes (n = 3/group, for grading see Supplementary Fig. 3). Original magnification ×400. Results from one of two independent experiments are shown. Data are displayed as mean ± SEM and analyzed by two-tailed Student t test. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.