As AML cells show approximately 2-fold reduction in TPL2 mRNA levels [4], mutational inactivation of p53 and cytoplasmic localization of NPM [2], it can be postulated that the TPL2/NPM/HDM2/p53 response might also, alone or in synergy with the RPL5/RPL11/5S rRNA/HDM2/p53 signaling pathway, inhibit progression of pre-neoplastic MDS cells to AML, a possibility that warrants further investigations. Here, NPM1 is linked to acute myeloid leukemia.