Molecular Correlates of Methotrexate in Childhood ALL
Molecular Correlates of Methotrexate in Childhood ALL
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.
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.
Inclusion Criteria:
Diagnosis of B-precursor or T-cell acute lymphoblastic leukemia
Banked diagnostic blast specimens are available from Childrens Oncology Group (COG) cellbank