Ricerc@Sapienza

Aberrant Notch signaling has been implicated in the development of several diseases, including T-cell acute lymphoblastic leukemia (T-ALL), a malignant disorder that originates from hematopoietic precursors committed to T-cell lineage. Survival rates in T-ALL patients have greatly improved in the last decades but still a substantial number of patients will relapse and die. An increased understanding of T-ALL biology has already translated into new prognostic biomarkers and has opened opportunities for the development of targeted therapies for the treatment of this disease. Recently, several studies suggest the role of the unfolded protein response (UPR) in acute leukemias. UPR is a conserved adaptive signaling pathway which tries to restore protein homeostasis mainly after Endoplasmatic Reticulum (ER) stress. It has been demonstrated that cancer cells are able to maintain malignancy by acquiring therapy resistance through its UPR signaling. Since several mutations of Notch3 protein have been recently identified, our main aim is to evaluate the role of Notch3 (N3) in sustaining UPR signaling in N3-overexpressing T-ALL cell lines.