Valutazione dellassociazione ATRA e INF nella Policitemia Verae Trombocitemia Essenziale.

Novella PuglieseUnit di Ematologia

Universit Federico II, Napoli

Shen et al PNAS 101: 5328-5335, 2004

LICs are very sensitive to ROS that are stronglyinduced both by ATO and anthracyclines butare less prone to differentiation process thanother hematopoietic progenitors

(Licht New Engl J Med 360: 928-930, 2009).

The pharmacologic enhancement of cyclic AMPsignaling could help leukemic celldifferentiation/apoptosis, thus compounds thatexploit this mechanism such the differentclasses of phosphodiesterases ininhibitors couldbe tested in combination therapy in non APLmalignancies (Altucci et al Nat Rev Drug Disc6: 793-810, 2007).

Pharmacologic levels of cAMP, induced by PDE4 orPDE5 confered onto retinoid X receptor (RXR)-selective agonists (rexinoids) the ability to induceterminal granulocyte differentiation and apoptosis ofATRA-insensitive PML-RARa negative leukemic celllines and AML patients blasts, irrespective of FABsubtype, karyotype, immunophenotype. It is worthmentioning that high cAMP levels block pro-survivalc-Raf signaling and stimulate proapoptotic D5 TRAILreceptor. Reviewed in Lunghi, Mazzera, Bonati,submitted.