Recent advances in the pathogenesis and management of juvenile myelomonocytic leukaemia.

Juvenile myelomonocytic leukaemia (JMML) is a fatal, mixed myeloproliferative and myelodysplastic disorder of early childhood. A number of significant advances have been achieved in recent years. The present review will focus on the pathogenesis and management of JMML. Specific defects in the RAS signalling pathway, which make JMML cells hypersensitive to granulocyte-macrophage colony-stimulating factor, are observed in at least two-thirds of patients with JMML: inactivation of NF1 or mutations in NRAS, KRAS2 or PTPN11. Allogeneic haematopoietic stem cell transplantation is currently the only treatment able to cure JMML, although the high postrelapse rate is of great concern. We also review molecularly targeted therapeutics that interfere with the disrupted activation of the RAS signal transduction pathway.