Studying Samples From Patients With T-Cell Acute Lymphoblastic Leukemia
RATIONALE: Studying samples of blood, tissue, and bone marrow from patients with cancer in the laboratory may help doctors identify learn more about biomarkers related to cancer. It may also help doctors to find better ways to treat cancer.
PURPOSE: This research studies samples from patients with T-cell acute lymphoblastic leukemia (T-ALL).
Genetic: gene expression analysis
Other: cell culture procedure
Other: flow cytometry
Other: laboratory biomarker analysis
Other: metabolic assessment
|Study Design:||Observational Model: Case-Only
Time Perspective: Retrospective
|Official Title:||Metabolic Pathways in T-Cell Acute Lymphoblastic Leukemia (T-ALL)|
- Metabolic status of primary T-ALL
- Effects of metabolic inhibition on metabolic stress pathways and apoptosis
- Metabolic inhibition interaction with chemotherapy or targeted drugs
|Study Start Date:||April 2012|
|Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
- Determine the metabolic status and regulation of primary T-cell acute lymphoblastic leukemia (T-ALL) relative to control resting peripheral T cells.
- Establish the effects of metabolic inhibition on metabolic stress pathways and apoptosis.
- Determine how metabolic inhibition interacts with chemotherapy or targeted therapy drugs to kill T-ALL cells.
OUTLINE: T-ALL samples cultured alone or with gamma secretase inhibitors (GSI) or PI3K inhibitors are analyzed for metabolic characteristics including glucose transporter 1 (Glut1) expression, mitochondrial mass, phospho-flow for 5' adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and mammalian target of rapamycin (mTOR) by flow cytometry. T-ALL samples and normal CD4+ T cells (control) are also exposed to ± 2-deoxyglucose or ± the glutaminolysis inhibitor media and analyzed for metabolic stress responses over time in particular, AMPK activation, autophagy (immunofluorescence for LC3-II processing), and BCL2-associated X protein (Bak) and Bax activation to indicate apoptosis. These cells (T-ALL and control) are then cultured with cyclophosphamide, dexamethasone, or the B-cell CLL/lymphoma 2 (Bcl-2) inhibitor, ABT-737, to determine cell death over time.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01581528
|Principal Investigator:||Jeffrey C. Rathmell, PhD||Duke Cancer Institute|