Relationship of MPO and NQO1 gene polymorphisms with susceptibility to acute leukemia / 中国实验血液学杂志

The aim of this study was to investigate the relationship of the gene polymorphisms of myeloperoxidase (MPO) and NAD (P) H: quinone oxidoreductase 1 (NQO1) with the susceptibility to acute leukemia (AL) in Chinese Gansu population. A 1:1 paired case-control study of 150 patients with acute leukemia and 150 cancer-free inpatients as a control was conducted to detect the polymorphisms of MPO and NQO1 by LDR techniques. The results showed that the MPO-463A genotype frequency in patient group was lower than that in control group, and there was significant difference of MPO (G-463A) genotype between patient group and control group (χ(2) = 11.828, P < 0.05, OR = 0.368, 95%CI = 0.205 - 0.610). The NQO1-609T genotype frequency in patient group was higher than that in control group, and there was significant difference of NQO1 (C-609T) genotype between patient group and control group (χ(2) = 17.931, P < 0.05, OR = 1.428, 95%CI = 1.237 - 3.339). The combined gene analysis showed that the AML risk in patients carrying the wild genotypes of MPO and NQO1 was dropped to 33.6%. It is concluded that the MPO and NQO1 gene polymorphisms are associated with susceptibility to AL. The AL risk may decrease in patients carrying MPO (G-463A) mutant gene (GA/AA), while the AL risk may increase in patients carrying NQO1 (C-609T) mutant gene (TC/TT). The combined effect of MPO and NQO1 wild genotypes may further decrease AL risk.

Relationship between polymorphisms of myeloperoxidase gene and susceptibility of acute leukemia in Chinese Gansu population / 中国实验血液学杂志

This study was aimed to explore the relationship between gene polymorphisms of myeloperoxidase (MPO) and the susceptibility of acute leukemia in Chinese Gansu population. G463A mutation of mpo gene was analyzed by polymerase chain reaction-ligase detection reaction (PCR-LDR) in 100 normal individuals (control group) and 100 patients with acute leukemia (AL group). The results showed that the a allele genotype and ga/aa genotype of mpo gene occurred more frequently in control group (28% and 54%) than those in AL group (19% and 31%) (p < 0.05). The AL risk for controls was decreased by 0.383-fold, compared with the individuals with gg genotype (95%CI = 0.215 - 0.682, p < 0.01). By further stratified analysis, the ga/aa genotype of mpo gene occurred more frequently in control group (54%) than those in AML group (28.2%) (p < 0.01). AML risk (95%CI = 0.157 - 0.546, p < 0.01) in the controls was decreased by 0.346-fold compared with the individual with gg genotype, however, the acute lymphoblastic leukemia (ALL) showed no significant difference from control group in the incidence of the allele a genotype and ga/aa genotype of mpo gene. It is concluded that mpo gene polymorphism is associated with susceptibility of acute myeloid leukemia in Chinese Gansu population. The risk of AML decreases in the persons carrying a allele, but mpo gene polymorphism is not associated with susceptibility of acute lymphoblastic leukemia.

Arsenic trioxide inhibits P-glycoprotein expression in multidrug-resistant human leukemia K562/ADM cell line that overexpresses mdr-1 gene and enhances their chemotherapeutic sensitivity / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of arsenic trioxide (As(2)O(3)) on the apoptosis and P-glyco-protein (P-gp) expression of multidrug-resistant human leukemia K562/ADM cells, and the combined effects of As(2)O(3) with conventional chemotherapeutic agents.</p><p><b>METHODS</b>Multidrug-resistant human leukemia cell line K562/ADM that overexpresses mdr-1 gene was used as the target cells. The cell proliferating activity was assessed with a MTT assay. Cell morphology was examined by light microscopy, confocal microscopy and electron-microscopy. P-gp expression, cell-cycle status were determined by flow cytometry.</p><p><b>RESULTS</b>K562/ADM cells were highly resistant to adriamycin, and cross-resistant to daunorubicin and etoposide. As(2)O(3) at concentrations of 0.5 to 20 micromol/L inhibited the proliferation of K562/ADM cells, and K562/ADM cells were more sensitive to As(2)O(3) than their parent K562 cells did. As(2)O(3) induced marked apoptosis of K562/ADM cells showed by typical apoptotic morphological changes and the appearance of high sub-G(1) cell population. As(2)O(3) significantly inhibited the P-gp expression in K562/ADM cells, and exerted a synergistic effect on the enhancement of the cell sensitivity to adriamycin, daunorubicin and etoposide.</p><p><b>CONCLUSION</b>As(2)O(3) induces growth-inhibition and apoptosis of multidrug-resistant K562/ADM cells, and augments synergistically the sensitivity of the cells to conventional chemotherapeutic agents via down-regulation of P-gp expression.</p>