T-ALL

Targeting the ER/UPR signalling in Notch3-overexpressing T-cell acute lymphoblastic leukemia.

Aberrant Notch signaling is involved in the development of several diseases, including T-cell acute lymphoblastic leukemia (T-ALL). A better knowledge of T-ALL biology 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. Juglone, a naturally-occurring naphtoquinone, is considered a promising anticancer agent for its strong activity against cancer cells in in vitro and in vivo models, including leukemia.

NF-κB1 Regulates Immune Environment and Outcome of Notch-Dependent T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric malignancy that arises from the transformation of immature T-cell progenitors and has no definitive cure. Notch signaling governs many steps of T cell development and its dysregulation represents the most common causative event in the pathogenesis of T-ALL. The activation of canonical NF-κB pathway has been described as a critical downstream mediator of Notch oncogenic functions, through the sustaining of tumor cell survival and growth.

Chalcones and chalcone-mimetic derivatives as Notch inhibitors in a model of T-cell Acute Lymphoblastic Leukemia

Based on hit-likeness and chemical diversity, a number of chalcones and chalcone-mimetic compounds were selected as putative Notch inhibitors. The evaluation of the antiproliferative effect combined with the inhibition of Notch1 expression in KOPTK1 cell line identified compound 18, featuring a tetrahydronaphthalene-based scaffold, as a new promising Notch-blocking agent.

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