mRNA expression profile of multidrug resistance genes in childhood acute lymphoblastic leukemia. Low expression levels associated with a higher risk of toxic death.

Full Abstract

BACKGROUND: Increased activity of multidrug resistance (MDR) genes has been associated with treatment failure in acute leukemias, although with controversial reports. The objective of the present study was to assess the expression profile of the genes related to MDR: ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP in terms of the clinical and biological variable and the survival of children with acute lymphoblastic leukemia (ALL). PROCEDURE: The levels of mRNA expression of the drug resistance genes ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP were analyzed by quantitative real-time PCR using the median values as cut-off points, in consecutive samples from 140 children with ALL at diagnosis. RESULTS: Expression levels of the ABCG2 gene in the patient group as a whole (P = 0.05) and of the ABCG2 and ABCC1 genes in patients classified as being at high risk were associated with higher rates of 5-year event-free survival (EFS) (P = 0.04 and P = 0.01). Expression levels of the ABCG2 gene below the median were associated with a greater chance of death related to treatment toxicity for the patient group as a whole (P = 0.009) and expression levels below the median of the ABCG2 and ABCC1 genes were associated with a greater chance of death due to treatment toxicity for the high-risk group (P = 0.02 and P = 0.03, respectively). CONCLUSION: The present data suggest a low participation of the drug efflux genes in treatment failure in patients with childhood ALL. However, the low expression of some of these genes may be associated with a higher death risk related to treatment toxicity.

Author information

Author/s: Cortez, Maria A A (MA); Scrideli, Carlos A (CA); Yunes, José A (JA); Valera, Elvis T (ET); Toledo, Sílvia R C (SR); Pavoni-Ferreira, Patrícia C B (PC); Lee, Maria L M (ML); Petrilli, Antônio S (AS); Brandalise, Silvia R (SR); Tone, Luiz G (LG);

Affiliation: Faculty of Medicine of Ribeirao Preto, Department of Genetics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.

Journal and publication information

Publication Type: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't

Journal: Pediatric blood & cancer (Pediatr Blood Cancer), published in United States. (Language: eng)

Reference: 2009-Dec; vol 53 (issue 6) : pp 996-1004

Dates: Created 2009/09/16; Completed 2009/10/13;

PMID: 19672972, status: MEDLINE (last retrieval date: 10/13/2009, IMS Date: )

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

ATP-Binding Cassette Transporters - genetics
Adolescent
Antineoplastic Combined Chemotherapy Protocols - therapeutic use; toxicity
Child
Child, Preschool
Gene Expression Profiling
Genes, MDR - genetics
Humans
Infant

Infant
Multidrug Resistance-Associated Proteins - genetics
Neoplasm Proteins - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; mortality
RNA, Messenger - analysis
Risk Assessment
Survival Analysis
Survival Rate
Treatment Failure

Associated Chemicals: ABCG2 protein, human (0) ; ATP-Binding Cassette Transporters (0) ; Multidrug Resistance-Associated Proteins (0) ; Neoplasm Proteins (0) ; RNA, Messenger (0) ; multidrug resistance-associated protein 1 (0)

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