Studying Samples From Patients With T-Cell Acute Lymphoblastic Leukemia

NCT ID: NCT01581528

Last Updated: 2016-05-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 15 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-04-30

Brief Summary

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

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.

Conditions

Leukemia

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Interventions

gene expression analysis

Intervention Type: GENETIC

cell culture procedure

Intervention Type: OTHER

flow cytometry

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

metabolic assessment

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey C. Rathmell, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Other Identifiers

COG-AALL12B5

Identifier Type: OTHER

Identifier Source: secondary_id

AALL12B5

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-00728

Identifier Type: REGISTRY

Identifier Source: secondary_id

AALL12B5

Identifier Type: -

Identifier Source: org_study_id