Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia
关键词
抽象
描述
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.
日期
| 最后验证: | 06/30/2020 |
| 首次提交: | 05/08/2009 |
| 提交的预估入学人数: | 05/08/2009 |
| 首次发布: | 05/11/2009 |
| 上次提交的更新: | 07/21/2020 |
| 最近更新发布: | 07/23/2020 |
| 实际学习开始日期: | 09/30/2006 |
| 预计主要完成日期: | 12/31/2099 |
状况或疾病
干预/治疗
Genetic: Group 1
Genetic: Group 1
Genetic: Group 1
Genetic: Group 1
Other: Group 1
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Group 1 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. | Genetic: Group 1 |
资格标准
| 有资格学习的年龄 | 15 Years 至 15 Years |
| 有资格学习的性别 | All |
| 取样方式 | Non-Probability Sample |
| 接受健康志愿者 | 是 |
| 标准 | 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 |
结果
主要结果指标
1. Correlation of 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 [Baseline]
2. Effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms on treatment outcome [Baseline]
次要成果指标
1. Association of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes with Pgp, MRP-1, and BCRP function and expression in pre-treatment blasts [Baseline]
2. Effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on Pgp, MRP-1, and BCRP function [Baseline]
3. Association of additional candidate genes relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicity [Baseline]
