Inositide signaling: Nuclear targets and involvement in myelodysplastic syndromes

Here we have reviewed the role of nuclear PLCβ1 signaling and namely its down-stream targets as well as the significance of inositide signaling, basically in the nucleus, in MDS blasts. As concerning myogenic differentiation, PLCβ1 along with the γ1 isoform, is essential for C2C12 myoblasts to become myotubes as judged by both molecular and morphological analysis. Both PLCs are capable of inducing, once overexpressed in their physiological compartment, the differentiation of C2C12 myoblasts by targeting specific regions of the cyclin D3 promoter even in the absence of insulin. When dealing with MDS it has been found that nuclear PLCβ1 has a specific role in MDS blasts and this is not only because of the presence of the mono-allelic deletion of its gene in high-risk patients who evolved in AML, but also because of its modulation, namely up-regulation, by means of azacitidine in high-risk responsive patients, which parallels the decrease of activated Akt. Indeed this seems interesting in the light of the fact that the Akt/mTOR pathway is critical for cell survival and proliferation in high-risk MDS patients, and that this signaling network could become an interesting therapeutic target for treating more advanced MDS patients.