CBL and juvenile myelomonocytic leukemia: Mutations in the linker region and RING finger domain of CBL impair the ability of Grb2 and SOS to suppress RAS signaling, and thereby over-activate RAS.65 CBL mutations have been found at high frequency (15%) in JMML and in 1% to 2% of adult AML.66,67 Recent studies also reported CBL mutations in KMT2A-rearranged patients (Fig. 2 and Supplemental Table 1, Supplemental Digital Content).36,39,41