A second, often subclonal, mutation occurs in less than half of JMML cases; this mutation can occur in another RAS pathway gene or in SETBP1, JAK3, SH3BP1, SH2B3, or components of the polycomb repressive complex 2, including EZH2 and ASXL1 [29, 30, 36]. Here, JAK3 is linked to juvenile myelomonocytic leukemia.