PTPN11 and Splenomegaly: In juvenile myelomonocytic leukemia (JMML), a malignant myeloproliferative neoplasia manifests as splenomegaly with consequential thrombocytopenia; mutations in the PTPN11 (SHP2) gene leads to the hyperactivation of ERK and AKT signaling pathways [52,53].