Abstract

We could recently show that the expression of the multidrug resistance-associated protein 3 (MRP3; ABCC3) is an important prognostic factor in ALL and in AML (

Blood
2003
;
102
:
4493
–8
and
Clin Cancer Res
2003
;
9
:
1083
–6
).

Lang et al. showed that the single nucleotide polymorphism −211C>T (NCBI SNP ID: rs4793665) in the promoter region of the MRP3 gene is associated with the expression of the gene in liver cells (

Pharmacogenetics
2004
;
14
:
155
–64
). They found that individuals who were homozygous for cytosine in position 211 showed higher levels of MRP3 mRNA and protein. Lang et al. also provided evidence that the polymorphism is located at a binding site for transcription factors and that the polymorphism affected the binding of such factors. This could explain the influence of the genotype on the transcription level of the gene.

Because of these findings, we hypothesized that the SNP −211C>T might also determine the expression of MRP3 in acute leukemia and therefore be an inborn determinant of drug resistance. In order to prove this hypothesis we analyzed this SNP in our previously described groups of ALL and AML patients.

The genotype was determined using a ready to use TaqMan® SNP Genotyping Assay and the ABI PrismTM 7700 Sequence Detector (Assay ID: C_27829307_10; Applied Biosystems, Foster City, CA, USA).

Samples from 139 patients were analyzed. The frequency of the genotypes was: TT = 32% (n=44), CC = 22% (n=31), and CT = 46% (n=64). We did not find any correlation between the genotype and the expression of MRP3 (p=0.44). The result was the same, when patients with AML, T-lineage ALL, and precursor B-lineage ALL were analyzed separately. We also did not find a correlation between the genotype and response to therapy or the chance of survival.

In conclusion, the SNP −211C>T in the promoter region of MRP3 does not have a major impact on the level of MRP3 gene expression in acute leukemia and it does not determine the response to therapy. Possibly, the putative transcription regulator which binds at this part of the MRP3 gene is not active in acute leukemia.

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