Modulation of glucocorticoid resistance in pediatric T - cell Acute Lymphoblastic 1 Leukemia by increasing BIM expression with the PI 3 K / mTOR inhibitor BEZ 235
نویسندگان
چکیده
Modulation of glucocorticoid resistance in pediatric T-cell Acute Lymphoblastic 1 Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235 2 3 Connor P. Hall , C. Patrick Reynolds, Min H. Kang 4 5 Cancer Center, Pharmacology and Neuroscience, Cell Biology & Biochemistry, Pediatrics, 6 Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 7 Lubbock, TX; 8 9 Correspondence: Min H. Kang, PharmD 10 Cell Biology & Biochemistry 11 School of Medicine, Texas Tech University Health Sciences Center 12 3601 4 Street STOP 9445, Lubbock, TX 79430 13 Phone: 806-743-2694; Fax: 806-743-2990 14 Email: [email protected] 15 16
منابع مشابه
Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235
Modulation of glucocorticoid resistance in pediatric T-cell Acute Lymphoblastic 1 Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235 2 3 Connor P. Hall , C. Patrick Reynolds, Min H. Kang 4 5 Cancer Center, Pharmacology and Neuroscience, Cell Biology & Biochemistry, Pediatrics, 6 Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 7 Lubbock...
متن کاملModulation of Glucocorticoid Resistance in Pediatric T-cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K/mTOR Inhibitor BEZ235.
PURPOSE The aim of our study is to evaluate the preclinical therapeutic activity and mechanism of action of BEZ235, a dual PI3K/mTOR inhibitor, in combination with dexamethasone in acute lymphoblastic leukemia (ALL). EXPERIMENTAL DESIGN The cytotoxic effects of BEZ235 and dexamethasone as single agents and in combination were assessed in a panel of ALL cell lines and xenograft models. The und...
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Glucocorticoids play a critical role in the therapy of lymphoid malignancies, including pediatric acute lymphoblastic leukemia (ALL), although the mechanisms underlying cellular resistance remain unclear. We report glucocorticoid resistance attributable to epigenetic silencing of the BIM gene in pediatric ALL biopsies and xenografts established in immune-deficient mice from direct patient expla...
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BACKGROUND Glucocorticoid (GC) resistance is frequently seen in acute lymphoblastic leukemia of T-cell lineage (T-ALL). In this study we investigate the potential and mechanism of using rapamycin to restore the sensitivity of GC-resistant T-ALL cells to dexamethasone (Dex) treatment. METHODS Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT)...
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Glucocorticoids are critical components of combination chemotherapy regimens in pediatric acute lymphoblastic leukemia (ALL). The proapoptotic BIM protein is an important mediator of glucocorticoid-induced apoptosis in normal and malignant lymphocytes, whereas the antiapoptotic BCL2 confers resistance. The signaling pathways regulating BIM and BCL2 expression in glucocorticoid-treated lymphoid ...
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