Expression of Gli1 in Adult Acute Lymphoblastic Leukemia and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of Hedgehog signaling transcription factor Gli1 in acute lymphoblastic leukemia (ALL) patients.</p><p><b>METHODS</b>The clinical specimens were obtained from 32 newly diagnosed and 6 relapsed ALL patients. Normal bone marrow cells from 15 healthy donors were used as controls. Real-time qPCR and Western blot were applied to detect Gli1 mRNA and protein expression in bone marrow mononuclear cells (BMMNC) of these samples respectively. The relation of Gli1 mRNA levels with clinical parameter was also evaluated.</p><p><b>RESULTS</b>The expression level of Gli1 mRNA in de novo and relapsed ALL patients was significantly higher than that in the normal controls (P < 0.05). There was no stalistically significant difference of the Gli1 mRNA expression between de novo and relapsed ALL cases (P > 0.05). In 24 de novo ALL patients with complete remission (CR) after induction chemotherapy, the levels of Gli1 mRNA were significantly reduced as compared with levels before treatment (P < 0.05). However, in 4 ALL patients without remission, no obvious difference of Gli1 mRNA levels were observed as compared with levels of Gli1 before treatment (P > 0.05). A positive correlation between the Gli1 mRNA expression level and white blood cell count (WBC) was found in the BMMNC of ALL patients (R = 0.725, P < 0.05). Similarly, Gli1 protein expression was significantly higher in the de novo and relapsed ALL cases compared with normal controls. The Gli1 protein level was down-regulated when the ALL patients was in CR.</p><p><b>CONCLUSION</b>The expression of Gli1 mRNA and protein has been found to be high in de novo and relapsed ALL patients, and the change of Gli1 expression maybe relate to therapeutic efficacy and prognosis of ALL patients.</p>

Decitabine inhibits cell proliferation and induces apoptosis of all-trans retinoid acid-resistant acute promyelocytic leukemia NB4-R2 cell line / 中国实验血液学杂志

The aim of this study was to investigate the proliferation-inhibitory and inducing apoptotic effects of decitabine (DAC) on acute promyelocytic leukemia NB4-R2 cells. Cell inhibitory rate was determined by cell proliferation and cytotoxicity assay (WST-1 assay) after NB4-R2 cells were treated with 0.01 - 0.5 µmol/L DAC for 24, 48 and 72 h. Apoptosis of NB4-R2 cells treated with 0.05 - 5 µmol/L DAC for 48 h was detected by flow cytometry with PI staining and AnnexinV/PI staining. Reverse transcription-PCR (RT-PCR) was used to determine the mRNA expression level of MDR1 gene encoding P-glycoprotein (P-gp). The results indicated that DAC (0.01 - 0.5 µmol/L) inhibited the proliferation of NB4-R2 cells in both time- and concentration-dependent manners. The IC(50) of DAC on the viability of NB4-R2 cells after treatment for 48 and 72 h were 0.089 and 0.064 µmol/L respectively. DAC (0.05 - 5 µmol/L) induced NB4-R2 cell apoptosis in dose-dependent manner with down-regulation of MDR 1 gene expression. It is concluded that a low concentration of DAC (< 0.5 µmol/L) inhibits cell proliferation, while higher concentration of DAC (1 or 5 µmol/L) induces apoptosis on NB4-R2 cells, accompanied with reduction of MDR1 levels.