Considering the clinical phenotypes associated with germline SH2B3 variants, it is puzzling that they can cause thrombocytosis or erythrocytosis in the absence of somatic mutations [28], while also cooperating with other driver mutations such as JAK2 or CALR to result in adult-type MPD [6, 7, 13, 14, 29], or PTPN11 to result in JMML. Here, SH2B3 is linked to juvenile myelomonocytic leukemia.