Nanoparticle Formulation to Improve the Efficacy of Radiation Therapy Against Radiation-resistant Leukemia

Abstract

Patients with B-precursor acute lymphoblastic leukemia (BPL) are often treated with TBI-based conditioning, followed by hematopoietic stem-cell transplantation (HSCT). However, the leukemic relapse in high-risk BPL patients remained the major cause of patient mortality (Gaynon et al., 2006, Balduzzi et al., 2014). The incidence of post-HSTC relapse correlated with the level of residual leukemia burden prior to total body irradiation (TBI), indicating the radiation-resistant population of BPL cells may have contributed to the relapse. STAT-3 signaling pathway, along with PI3-K and NFkB pathways, regulates the cell survival after exposure to radiation-induced oxidative stress (Uckun et al., 2010), therefore contributes to the radiation resistance of BPL cells. Spleen tyrosine kinase (SYK), a key regulator of STAT-3, was chosen as the main target of reducing the radiation resistance (Mocsai et al., 2010). The authors identified C61, a small-molecule chemical compound inhibitor for SYK phosphorylation, which sensitized the resistant BPL cells toward radiation.