Mutations in the Cbl family RING finger domain or linker sequence constitute important pathogenic lesions associated with not only preleukaemic CMML, juvenile myelomonocytic leukeamia (JMML), and other myeloproliferative neoplasms (MPN), but also progression to AML, suggesting that impaired degradation of activated tyrosine kinases constitutes an important cancer mechanism (35). This evidence concerns the gene CBL and juvenile myelomonocytic leukemia.