CXCR4 and Splenomegaly: Recently, JAK2 activation in MPL-mutant cells was found to support the CXCL12/CXCR4 pathway and activate downstream JAK-STAT, PI3K/AKT, and RAS/MAPK activation pathways, leading to the expansion of malignant clones, EMH, and splenomegaly in MF patients [32].