Trial Information

Multidrug Resistance Protein Gene Polymorphisms in Acute Myeloid Leukemia. A CALGB Leukemia Tissue Bank Project

OBJECTIVES:

Primary

- Correlate common single nucleotide polymorphisms (SNPs) and haplotypes of the 3
multidrug resistance genes (P-glycoprotein [Pgp], multidrug resistance-associated
protein (MRP-1), and breast cancer resistance protein [BCRP]) with treatment outcome in
patients with acute myeloid leukemia (AML).

- Determine the effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms
and haplotypes on treatment outcome in younger patients enrolled on CALGB-9621 or
CALGB-19808.

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

Secondary

- Determine whether ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes are associated
with Pgp, MRP-1, and BCRP function and expression in pre-treatment blasts from patients
with AML.

- Determine the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on Pgp,
MRP-1, and BCRP function, according to the methods used in CALGB-9760, in younger
patients enrolled on CALGB-9621 or CALGB-19808.

- Determine the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on Pgp,
MRP-1, and BCRP function, according to the methods used in CALGB-9760, in older
patients enrolled on CALGB-9720.

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

OUTLINE: This is a multicenter, retrospective study.

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.