Response or Resistance to Chemotherapy in Young Patients With Acute Lymphoblastic Leukemia Treated With Methotrexate

Study Overview
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Brief Summary
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This laboratory study is looking at response or resistance to chemotherapy in young patients with acute lymphoblastic leukemia treated with methotrexate. Studying samples of tumor tissue in the laboratory from patients with cancer may help doctors learn more about changes that occur in DNA and drug resistance in patients.

Detailed Description
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OBJECTIVES: I. Determine the molecular basis for human reduced folate carrier (hRFC) transcripts in B-precursor and T-cell acute lymphoblastic leukemia (ALL) blasts obtained from children with newly diagnosed ALL subsequently treated with methotrexate. II. Correlate hRFC expression in these specimens with methotrexate transport and sensitivities. III. Determine the roles of high frequency gene/transcript variants for hRFC as determinants of response and resistance to methotrexate in these patients. IV. Determine the roles of multidrug resistance-associated proteins as determinants of response and resistance to methotrexate and mercaptopurine in these patients. OUTLINE: This is a multicenter study. Tumor diagnostic specimens from patients who subsequently failed therapy within 4 years of diagnosis or who did not fail therapy within 4 years of diagnosis (control patients) are obtained from the Children's Oncology Group cellbank. Specimens are studied for molecular determinants of human reduced folate carrier (hRFC) gene expression and gene sequence alterations using reverse transcriptase-polymerase chain reaction (RT-PCR), thymidylate synthase inhibition assay, Rnase protection assay, or 5'RACE. Multidrug resistance proteins are also studied by RT-PCR. A certificate of confidentiality protecting the identity of research participants in this project has been issued by the National Cancer Institute.

Official Title
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Molecular Correlates of Methotrexate in Childhood ALL

Conditions
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B-cell Childhood Acute Lymphoblastic Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Recurrent Childhood Acute Lymphoblastic Leukemia, T-cell Childhood Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of B-precursor or T-cell acute lymphoblastic leukemia Newly diagnosed disease subsequently treated with methotrexate Banked diagnostic blast specimens are available from Childrens Oncology Group (COG) cellbank

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm I<br>Tumor diagnostic specimens from patients who subsequently failed therapy within 4 years of diagnosis or who did not fail therapy within 4 years of diagnosis (control patients) are obtained from the Children's Oncology Group cellbank. Specimens are studied for molecular determinants of human reduced folate carrier (hRFC) gene expression and gene sequence alterations using reverse transcriptase-polymerase chain reaction (RT-PCR), thymidylate synthase inhibition assay, Rnase protection assay, or 5'RACE. Multidrug resistance proteins are also studied by RT-PCR. | Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular basis for human reduced folate carrier (hRFC) transcripts |  | Up to 4 years | 
| Correlation of hRFC expression and methotrexate transport and sensitivities |  | Up to 4 years | 
| High frequency gene/transcript variants for hRFC in relation to response and resistance to methotrexate |  | Up to 4 years | 
| Multidrug resistance-associated proteins in relation to response and resistance to methotrexate and mercaptopurine |  | Up to 4 years |