Aptose Biosciences Inc (APTO)

[Tartiaboy]

NPM1 is mutated in approximately 35% of AML cells. Unmutated NPM1 shuffles between the nuceolus and the cytoplasm. Mutated NPM1 is predominantly found in the cytoplasm because of the loss of nucleolus localization signal. NPM1 binds a protein call HEXIM1. Mutated NPM1 can sequester most of the HEXIM1 in the cytoplasm.

Hexim1 is a key suppressor of pTEFb and a stabilizer of p53 in the nucleous. Loss of Hexim1 from the nucleous leads to activation of pTEFb (leading to gene transcription) and destabilization of p53 ( a gene expression repressor). i.e. in simplistic terms loss of control over gene transcription and malignancy.

Of course this is a very simplistic summary. You can read relevant articles that give much greater details. Try googling; MPM1 HEXIM1; or HEXIM1 AML, or NPM1 pTEFb.

AML cells with the common DNMT3A and NPM1 mutants are generally pre-AML. Once additional mutations such as Flt3 come into play the AML becomes more aggressive. ie. DNMT3a and NPM1mutations set the stage for the signaling pathways.