Kotecha N, Flores NJ, Irish JM et al.
Stanford University School of Medicine, Stanford, CA, USA.
Cancer Cell 2008;14:335–43.
Editor’s note: Juvenile myelomonocytic leukemia (JMML) is a clonal myelo-proliferative disorder (MPD) characterized at the molecular level by frequent dysregulation of RAS signaling. This aberrant signaling occurs through mutations of a number of different genes involved in this pathway, including protein tyrosine phosphatase, non-receptor type 11 (
PTPN11),
NRAS,
KRAS, and neurofibromin 1 (
NF1). Another characteristic feature of JMML is
in vitro hypersensitivity to granulocyte–macrophage colony-stimulating factor (GM-CSF), which signals through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Therefore, it is possible that interaction between RAS and JAK-STAT signaling may be important in the pathogenesis of this disorder. With recent advances in flow cytometry, cell signaling pathways may be examined at the single cell level, and the present authors used this state-of-the-art technology to investigate the relationship between RAS and the JAK-STAT pathway in JMML.