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Treatment of MDS patients with recombinant human erythropoietin and the role of GSTs.

Abstract：

:Glutathione S-transferases (GSTs) are a group of enzymes involved in the detoxification process of carcinogens and other substances. The genes encoding isoenzymes M1 and T1 have "null" alleles, which are polymorphic in humans. Our purpose was to examine whether the GSTM1 and GSTT1 homozygous null genotypes have an impact on the response to recombinant human erythropoietin (rhuEpo) treatment in MDS patients. We analyzed lymphocyte DNA samples from 27 patients with all types of myelodysplastic syndromes (MDS) at the time of diagnosis. All patients were scheduled to receive rHuEpo in doses of 150 u/Kg/day for a period of 12 weeks in order to obtain and maintain stable responses. A multiplex polymerase chain reaction (PCR) was used to genotype both GSTM1 and GSTT1 simultaneously, in responders and non-responders to rhuEpo with respect to various pretreatment parameters: haemoglobin, white blood cell count, platelets, serum erythropoietin, transfusion requirements and bone marrow blasts. The data obtained were evaluated by chi2 test and odds ratio were extracted. Twelve out of 27 evaluated patients demonstrated an erythroid response (44%). Nine out of the 12 patients (75%) responding after 12 weeks of treatment had GSTM1 null genotype (OR=3.4). In contrast, only 1 responder (8.3%) was homozygotes of GSTT1 null genotype. Furthermore, no statistically significant difference in the response rate of the different MDS subgroups was observed. Our results suggest that a treatment with rHuEpo may be effective in achieving a stable erythroid response in MDS patients who carry an homozygous deletion of the GSTM1 gene.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Tsabouri SE,Georgiou I,Katsaraki A,Bourantas KL

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

417-24

issue

3

eissn

0392-9078

issn

1756-9966

journal_volume

23

pub_type

杂志文章

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