Characterization of a patient with concurrent BRAF-mutant melanoma and NRAS-mutant leukemia treated intermittently with combined BRAF and MEK inhibition provides new insights into the potential clinical and molecular effects of this therapeutic strategy.
None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAFV600E variant, including 38 patients with splenic marginal-zone lymphomas or unclassifiable splenic lymphomas or leukemias.
The BRAF kinase is mutated, typically Val 600→Glu (V600E), to induce an active oncogenic state in a large fraction of melanomas, thyroid cancers, hairy cell leukaemias and, to a smaller extent, a wide spectrum of other cancers.
The ERK1/2 (extracellular signal-regulated kinase 1 and 2) pathway, comprising the protein kinases RAF (v-raf-1 murine leukemia viral oncogene homolog 1), MEK1/2 (mitogen-activated protein kinase or ERK kinase 1 and 2) and ERK1/2 is frequently de-regulated in human cancers, due to mutations in RAS or BRAF (v-raf-1 murine leukemia viral oncogene homolog B1).