Mutations clustered in the linker region or RING finger domain of CBL, and rarely CBL-B, which abrogate E3 activity, have been identified in a subset of patients with myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN), chronic myelomonocytic leukemia or juvenile myelomonocytic leukemia [38–44]. Here, CBL is linked to myelodysplastic syndrome.