Juvenile myelomonocytic leukaemia is a heterogeneous disease caused by constitutional activation of the Ras signal transduction pathway. The clinical course of the disease is variable and non-specific. In the majority of patients prompt hematopoietic stem cell transplantation is necessary for long-term survival, whereas in a minority the disease will resolve without treatment. In more than 90% of the patients, mutations in one or more of the following genes can be found (somatic NRAS, KRAS and PTPN11, germline NF1 and CBL). However, these canonical mutations are insufficient to explain the phenotypic heterogeneity of this disease. More recently, secondary mutations, non-coding RNA expression, and genomic DNA methylation have led to a better understanding of the pathobiology of the disease, and shown to play a role in the classification and prognostication of this rare disease. In addition, this novel information has been crucial for novel drug development and introduction of novel patient-tailored therapies, which are currently being tested in vitro or in vivo in clinical trials.
(BELG J HEMATOL 2020;11(2):49–55)