Gene Expression in Tissue From Patients With Acute Lymphoblastic Leukemia

Genetic Risk Classes in Adult Acute Lymphocytic Leukemia

RATIONALE: Studying the genes expressed in samples of tumor tissue from patients with cancer may help doctors identify biomarkers related to cancer.

PURPOSE: This laboratory study is looking at gene expression in tissue from patients with acute lymphoblastic leukemia enrolled in clinical trial ECOG-2993.

OBJECTIVES:

• Identify genes involved in specific biologic processes or molecular functions that contribute to the mechanisms by which the BCR/ABL tyrosine kinase induces a leukemic phenotype using RNA banked from patients with BCR/ABL-positive acute lymphoblastic leukemia (ALL) enrolled on ECOG-2993.
• Compare patterns of mRNA expression of BCR/ABL fusion protein in patients with B-lineage ALL vs patients with ALL and no cytogenetic abnormalities enrolled on ECOG-2993.
• Determine both shared and differing expression patterns in patients with BCR/ABL-positive and cytogenetically negative ALL with respect to achievement of complete remission and duration of disease-free and overall survival.

OUTLINE: This is a multicenter study.

Total RNA is isolated from stored tissue samples and integrity is verified by reverse transcription-polymerase chain reaction (RT-PCR). cDNA libraries are created from total RNA and gene expression is analyzed via microarray analysis.

Genes of interest are further analyzed by flow cytometry and RT-PCR.

PROJECTED ACCRUAL: A total of 137 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of acute lymphoblastic leukemia

• Tissue banked on protocol ECOG-2993 meeting the following criteria:

  • Leukemic blast cell population immunophenotyped in detail (e.g., including CD25) in ECOG's Immunophenotyping Reference Laboratory

  • Flow cytometric analysis of gated blast cells reveals association with the B-cell lineage

  • Mononuclear cell fraction used for RNA isolation contains 75-99% blasts (median 85%)

  • Negative for TEL/AML1, MLL/AF4, and E2A/PBX1 by qualitative reverse transcription-polymerase chain reaction (RT-PCR)

  • No FLT3 gene mutations

  • BCR/ABL-positive samples meeting the following criteria:

    • Presence of t(9;22)(q34;q11) by standard cytogenetics
    • Detection of either p190 BCR/ABL or p210 BCR/ABL transcripts by qualitative RT-PCR

  • Patients with genetic risk factors must meet the following criterion:

    • Only a normal diploid karyotype is present in ≥ 15 metaphases by standard cytogenetics

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• Not specified