Here we showed that (a) not only human myeloid (K562) and lymphoid (MOLT-4) cell lines but also primary cells from leukemia patients are highly sensitive to growth inhibition by WithaD in a dose and time dependant manner; (b) WithaD-mediated apoptosis was through the activation of N-SMase 2 and accumulation of ceramide content and (c) ceramide activate MKK group of proteins, leading to JNK and p38MAPK phosphorylation, resulting in their cooperative action to transduce the death signal. Here, MAPK8 is linked to leukemia.