SMPD3 and leukemia: 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.