Here we show that FLT3-ITD activates NTKDs of RSK1 and RSK2 distinctively in contrast to BCR/ABL, and that RSK1 predominantly mediates signaling required for proliferation and survival of FLT3-ITD-dependent, but not BCR/ABL-dependent, leukemic cells, including primary AML cells from one patient we could examine. This evidence concerns the gene FLT3 and acute myeloid leukemia.