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

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

- Newly diagnosed disease subsequently treated with methotrexate

- Banked diagnostic blast specimens are available from Childrens Oncology Group (COG)
cellbank