Strategic Role of Nuclear Inositide Signalling in Myelodysplastic Syndromes Therapy

Title:Strategic Role of Nuclear Inositide Signalling in Myelodysplastic Syndromes Therapy

Volume: 14 Issue: 11

Author(s): Lucia Manzoli, Sara Mongiorgi, Cristina Clissa, Carlo Finelli, Anna Maria Billi, Alessandro Poli, Marilisa Quaranta, Lucio Cocco and Matilde Y. Follo

Affiliation:

Keywords: Akt, azacitidine, erythropoietin, erythroid differentiation, myelodysplastic syndromes, myeloid differentiation, nuclear inositides, phospholipase Cβ1.

Abstract: Nuclear inositide signalling is implicated in normal and pathological cell proliferation and differentiation in several distinct models. Among the key molecules of nuclear inositide pathways, phosphoinositide-phospholipase (PI-PLC) C β1 is essential for regulating hematopoiesis, particularly along myeloid and erythroid lineage. Moreover, Akt activation is associated with protein synthesis, via mTOR pathway, and with erythroid induction, through PI-PLCγ1 activation. Myelodysplastic syndromes (MDS) are a series of heterogeneous diseases characterized by ineffective hemopoiesis, with a variable risk of evolution into acute myeloid leukemia (AML). Therapeutic approaches for MDS include demethylating agents, such as azacitidine, aiming at reducing cell proliferation, and erythropoietin, useful for sustaining a normal erythropoiesis. In the last few years, a role for nuclear inositide signalling as a therapeutic target in MDS has been disclosed, in that PI-PLCβ1 increase is associated with azacitidine responsiveness, even when this drug is used in combination with other agents, and Akt is specifically activated in MDS at higher risk of AML evolution. On the other hand, recent data demonstrated that inositide signalling can also be involved in erythroid therapy, given the inhibitory effect of erythropoietin on PI-PLCβ1 and the activation of Akt/PI-PLCγ1 pathway, following the administration of erythropoietin. Here, we review the strategic role of nuclear inositide signalling in MDS, in pathogenesis and therapy.

Cite this article as:

Manzoli Lucia, Mongiorgi Sara, Clissa Cristina, Finelli Carlo, Billi Maria Anna, Poli Alessandro, Quaranta Marilisa, Cocco Lucio and Follo Y. Matilde, Strategic Role of Nuclear Inositide Signalling in Myelodysplastic Syndromes Therapy, Mini-Reviews in Medicinal Chemistry 2014; 14 (11) . https://dx.doi.org/10.2174/1389557514666141013125936