Class I/II Histone Deacetylase Inhibitors Are a Potential Therapeutic For Notch-1 Driven T Cell Acute Lymphoblastic Leukemia

Abstract

Abstract Introduction Although T cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease, mutations resulting in activation of the Notch-1 signalling pathway are present in over 50% of patients, thus defining Notch signaling as a central player in T-ALL disease regulation. Furthermore, despite improvement in remission rates following conventional chemotherapeutics, the prognosis for T-ALL remains poor due to disease relapse, which is often refractory to the initial therapies. Inhibitors against the γ-secretase complex, which is part of intracellular Notch-1 (ICN1) signalling, have so far shown limited efficacy and a..