NOTCH1 Represses MCL-1 Levels in GSI-resistant T-ALL, Making them Susceptible to ABT-263

• Published in: Clinical cancer research Vol. 25; no. 1; pp. 312 - 324
• Main Authors: Dastur, Anahita, Choi, AHyun, Costa, Carlotta, Yin, Xunqin, Williams, August, McClanaghan, Joseph, Greenberg, Max, Roderick, Justine, Patel, Neha U, Boisvert, Jessica, McDermott, Ultan, Garnett, Mathew J, Almenara, Jorge, Grant, Steven, Rizzo, Kathryn, Engelman, Jeffrey A, Kelliher, Michelle, Faber, Anthony C, Benes, Cyril H
• Format: Journal Article
• Language: English
• Published: United States 01.01.2019
• Subjects: Amyloid Precursor Protein Secretases - antagonists & inhibitors; Amyloid Precursor Protein Secretases - genetics; Aniline Compounds - pharmacology; Animals; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Heterografts; Humans; Mechanistic Target of Rapamycin Complex 1 - genetics; Mice; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Receptor, Notch1 - genetics; Signal Transduction - drug effects; Sulfonamides - pharmacology

Effective targeted therapies are lacking for refractory and relapsed T-cell acute lymphoblastic leukemia (T-ALL). Suppression of the NOTCH pathway using gamma-secretase inhibitors (GSI) is toxic and clinically not effective. The goal of this study was to identify alternative therapeutic strategies f...