Hematology-in-Focus session: NPM1 in AML

He thinks that NPM1 must be considered as a tumor suppressor gene, regulating P53 stability via inhibition of MDM2 and stabilization of ARF protein. He showed the results obtained with NPM hypomorphic mutants and these experiments suggest that NPM1 is a haplosufficient tumor suppressor gene. Interestingly, NPM heterozygote mice developed MDS and later AML or CML, thus making an interesting murine model to evaluate new therapeutics.

Dr Falini presented the structural modifications of mutated NPM1 protein and the consequences in the cells, leading to the delocalization from the nucleus and the abnormal export of both normal and mutated NPM in the cytoplasm. He showed thatmutated NPM is present in all myeloid lineages and not in lymphocytes. This implies that the original mutation occurred in an immature myeloid progenitor.