Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To investigate the association of common single nucleotide polymorphisms (SNPs) and
haplotypes of the three multidrug resistance (MDR) genes with treatment outcome in the
clinical studies.

II. To assess the effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms and
haplotypes on treatment outcome in younger patients enrolled on Cancer and Leukemia Group B
(CALGB) 9621 and 19808.

III. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on
treatment outcome in older patients enrolled on CALGB 9720.

SECONDARY OBJECTIVES:

I. To test the hypothesis that ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes are
associated with phosphoglycolate phosphatase (Pgp), multidrug resistance protein 1 (MRP-1),
and ATP-binding cassette, sub-family G (WHITE), member 2 (Junior blood group) (BCRP) function
and expression in pre-treatment blasts from acute myeloid leukemia (AML) patients.

II. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on PGP,
MRP-1, and BCRP function through CALGB 9760 in younger patients enrolled on CALGB 9621 and
19808.

III. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on PGP,
MRP-1, and BCRP function through CALGB 9760 in older patients from CALGB 9720.

IV. To conduct an exploratory analysis of the association of additional candidate genes
relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicity.

OUTLINE:

Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are
used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2,
and other candidate genes. Multidrug resistance (MDR) protein expression and function are
also analyzed using leukemia blast cells from patients enrolled on CALGB-9760.

PROJECTED ACCRUAL: Tissue samples from over 600 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Diagnosis of acute myeloid leukemia

- Treated on protocols CALGB-9621, CALGB-9720, or CALGB-19808

- Registered on the mandatory companion Leukemia Tissue Bank Protocol CALGB-9665

- Registration on another companion trial, CALGB-9760, (Multidrug Resistance
Studies in Acute Leukemia) allowed

PATIENT CHARACTERISTICS:

- Not specified

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics