Studying Samples From Patients With T-Cell Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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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).

Detailed Description
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OBJECTIVES: 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.

Official Title
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Metabolic Pathways in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

Conditions
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Leukemia

Intervention / Treatment
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* Genetic: gene expression analysis
* Other: cell culture procedure
* Other: flow cytometry
* Other: laboratory biomarker analysis
* Other: metabolic assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Sample from patients diagnosed with T-ALL Samples from independent healthy donors obtained through the Gulf Coast Regional Blood Center (controls) PATIENT CHARACTERISTICS: Not specified PRIOR CONCURRENT THERAPY: Not specified
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: gene expression analysis|nan|
|Other: cell culture procedure|nan|
|Other: flow cytometry|nan|
|Other: laboratory biomarker analysis|nan|
|Other: metabolic assessment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic status of primary T-ALL |  |  | 
| Effects of metabolic inhibition on metabolic stress pathways and apoptosis |  |  | 
| Metabolic inhibition interaction with chemotherapy or targeted drugs |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-cell childhood acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia, T-cell adult acute lymphoblastic leukemia, untreated childhood acute lymphoblastic leukemia