The role of ABC-transporter gene polymorphisms in chemotherapy induced immunosuppression, a retrospective study in childhood acute lymphoblastic leukaemia

Dániel J Erdélyi; Eniko Kámory; Anna Zalka; Agnes F Semsei; Béla Csókay; Hajnalka Andrikovics; Attila Tordai; Gábor Borgulya; Edina Magyarosy; Ilona Galántai; György Fekete; András Falus; Csaba Szalai; Gábor T Kovács

doi:10.1016/j.cellimm.2007.02.007

The role of ABC-transporter gene polymorphisms in chemotherapy induced immunosuppression, a retrospective study in childhood acute lymphoblastic leukaemia

Cell Immunol. 2006 Dec;244(2):121-4. doi: 10.1016/j.cellimm.2007.02.007. Epub 2007 Apr 16.

Authors

Dániel J Erdélyi¹, Eniko Kámory, Anna Zalka, Agnes F Semsei, Béla Csókay, Hajnalka Andrikovics, Attila Tordai, Gábor Borgulya, Edina Magyarosy, Ilona Galántai, György Fekete, András Falus, Csaba Szalai, Gábor T Kovács

Affiliation

¹ Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.

PMID: 17434155
DOI: 10.1016/j.cellimm.2007.02.007

Abstract

We examined the association of functional ABCB1 (MDR1) and ABCG2 (BCRP) polymorphisms with acute side effects of chemotherapy. Analyses were performed on clinical data from 138 patients treated with the ALL-BFM-95 protocol implying several substrates of these transporters. ABCB1 3435T>C, 2677G>T/A 1236C>T and ABCG2 421C>A genotypes were determined. A higher proportion of ABCB1 3435TT patients suffered excessive infectious complications than those harbouring at least one C allele (OR=2.5, p=0.03) during the whole half-year-long intensive phase of chemotherapy. Weaker associations were calculated when ABCB1 1236T-2677T-3435T haplotype homozygotes were tested against the remaining part of the population (OR=2.3, p=0.09). During the reinduction phase of therapy, the occurrence of severe leukocytopenia was similar among ABCB1 genotype groups. The frequency of any toxicities were not shown to differ according to the ABCG2 421C>A genotype. Our data suggest that the ABCB1 3435T>C genotype is associated with the infectious complications of the applied chemotherapy regimen.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics*
ATP-Binding Cassette Transporters / immunology*
Adolescent
Antineoplastic Agents / adverse effects*
Antineoplastic Agents / therapeutic use
Child
Child, Preschool
Cohort Studies
Genotype
Humans
Infant
Neoplasm Proteins / genetics*
Neoplasm Proteins / immunology*
Opportunistic Infections / immunology
Organic Anion Transporters / genetics*
Organic Anion Transporters / immunology*
Polymorphism, Single Nucleotide
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
Retrospective Studies

Substances

ABCB1 protein, human
ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Antineoplastic Agents
Neoplasm Proteins
Organic Anion Transporters