Issue Archive

AF6 is a cytoplasmic protein with two distinctive features: one single PDZ and two RAS-interacting (RA) domains. These characteristics enable AF6, either alone or when fused to MLL, to modulate multiple signal transduction pathways in vivo, especially those involving RAS. The authors demonstrate that MLL-AF6 affects AF6 localization in t(6;11) myeloid leukemia cells in order to aberrantly activate RAS (green) and its downstream signaling to empower the tumorigenic potential. The silencing of MLL-AF6 relocalizes the AF6 protein back into the cytoplasm, leading to reduction of both RAS levels and activity. These results imply that RAS may play a crucial oncogenic role in this subtype of AML. See the article by Manara et al on page 263.