Impact of ABC single nucleotide polymorphisms upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia

被引：31

作者：

Eduardo Megias-Vericat, Juan ^{[1
,2
]}

Montesinos, Pau ^{[3
]}

Jose Herrero, Maria ^{[1
]}

Moscardo, Federico ^{[3
]}

Boso, Virginia ^{[1
,2
]}

Rojas, Luis ^{[1
,5
]}

Martinez-Cuadron, David ^{[3
]}

Hervas, David

Boluda, Blanca ^{[3
]}

Garcia-Robles, Ana ^{[2
]}

Rodriguez-Veiga, Rebeca ^{[3
]}

Martin-Cerezuela, Maria ^{[2
]}

Cervera, Jose ^{[3
]}

Sendra, Luis ^{[4
,6
]}

Sanz, Jaime ^{[3
,7
]}

Miguel, Antonio ^{[4
]}

Lorenzo, Ignacio ^{[3
]}

Luis Poveda, Jose ^{[2
,6
]}

Angel Sanz, Miguel ^{[3
]}

Alino, Salvador F. ^{[1
,4
]}

机构：

[1] Hosp Univ & Politecn La Fe Avda, Inst Invest Sanataria La Fe & Area Medicamento, Unidad Farmacogenet, Fernando Abril Martorell 106, Valencia 46026, Spain

[2] Hosp Univ & Politecn La Fe Avda, Area Medicamento, Serv Farm, Valencia, Spain

[3] Hosp Univ & Politecn La Fe Avda, Serv Hematol & Hemoterapia, Valencia, Spain

[4] Univ Valencia Avda, Fac Med, Dept Farmacol, Valencia, Spain

[5] Pontificia Univ Catolica Chile Avda, Dept Internal Med, Fac Med, Santiago, Chile

[6] Inst Investigaci Sanataria Fe Avda, Unidad Bioestadist, Valencia, Spain

[7] Hosp Univ & Politecn La Fe Avda, Area Medicamento, Unidad Farmacol Clin, Valencia, Spain

来源：

LEUKEMIA & LYMPHOMA | 2017年 / 58卷 / 05期

关键词：

Transporter; polymorphism; ABC; acute myeloid leukemia; efficacy; toxicity; anthracyclines; idarubicin; SNP; CANCER RESISTANCE PROTEIN; P-GLYCOPROTEIN; GENE POLYMORPHISMS; TREATMENT OUTCOMES; PROGNOSTIC VALUE; CHINESE PATIENTS; LOW EXPRESSION; MDR1; GENE; SURVIVAL; TRANSPORTER;

D O I：

10.1080/10428194.2016.1231405

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Anthracycline uptake could be affected by efflux pumps of the ABC family. The influence of 7 SNPs of ABC genes was evaluated in 225 adult de novo acute myeloid leukemia (AML) patients. After multivariate logistic regression there were no significant differences in complete remission, though induction death was associated to ABCB1 triple variant haplotype (p=.020). The ABCB1 triple variant haplotype was related to higher nephrotoxicity (p=.016), as well as this haplotype and the variant allele of ABCB1 rs1128503, rs2032582 to hepatotoxicity (p=.001; p=.049; p<.001). Furthermore, the variant allele of ABCC1 rs4148350 was related to severe hepatotoxicity (p=.044), and the variant allele of ABCG2 rs2231142 was associated to greater cardiac (p=.004) and lung toxicities (p=.038). Delayed time to neutropenia recovery was observed with ABCB1 rs2032582 variant (p=.047). This study shows the impact of ABC polymorphisms in AML chemotherapy safety. Further prospective studies with larger population are needed to validate these associations.

引用

页码：1197 / 1206

页数：10

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