A Preliminary Exploration on the Pathogenesis of Osteopenia in Patients with Hemophilia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the influencing factors and pathogenesis of osteopenia in the patients with hemophilia.</p><p><b>METHODS</b>Twenty-three patients with hemophilia were admitted in the hospital affiliated to North China University of Science and technology from March to August 2015, including 13 severe cases, 10 mild and moderate cases. All the patients accepted the detection of serum I collagen cross-linking N terminal peptide (NTX I), osteoprotegerin (OPG), bone alkaline phosphatase (BALP), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β1 (TGF-β1), the score scale of activity ability was recorded according to the criteria published by the U.S. Center for disease prevention and control in 2002, and 21 patients received the measurement of bone mineral density. According to the World Health Organization (WHO) definition, the clinical significance of bone mineral density (BMD) was assessed by measuring the Z level.</p><p><b>RESULTS</b>Z level>-2 was recorded in 10 cases, Z≤-2 was recorded in 11 cases; the levels of body mass index (BMI) and human bone alkaline phosphatase (BALP) reflecting bone formation in 11 cases (Z≤-2) were lower than there in 10 cases (Z>-2) (P<0.05); the levels of BALP (r=0.489, P<0.05), IGF (r=0.538, P<0.05) and BMI (r=0.572, P<0.01) positively correlated significantly with BMD (P<0.05); the levels of bFGF (r=0.570, P<0.01) and OPG (r=0.505, P<0.05) positively correlated with NTX I, indicating bone destruction (P<0.05); the score of activity ability of severe patients was significantly lower than that of mild and moderate cases (P<0.05), BMD levels of these 2 groups were not statistically different (P>0.05).</p><p><b>CONCLUSION</b>The BMD level does not correlate with the clinial grouping of hemophilia, the low body mass index may be a risk factor for bone lose; the mechanism of hemophilia patient's bone lose may be related with the decrease of osteogenic activity, the IGF can prevent bone lose in hemophilia, the bFGF and OPG can promote bone metabolism of the patients with hemophilia.</p>

Effects of STI571 combined with As₂O₃ on proliferation, apoptosis and caspase 3, Bcl-xL expression of K562 cells / 中国实验血液学杂志

This study was aimed to explore the effects of STI571 alone or with As₂O₃ on proliferation, apoptosis and caspase 3, bcl-xL mRNA expression of K562 cells, and the molecular mechanism of As₂O₃ enhancing the anti-leukemia effect of STI571 so as to provide the scientific basis for clinical treatment of chronic myeloid leukemia. The effect of drugs on proliferation of K562 cells was assayed by MTT method, the apoptosis rate of K562 cells was detected by flow cytometry with Annexin V/PI double staining, the caspase 3, bcl-xL mRNA expressions of K562 cells were determined by real time quantitative PCR. The results showed that STI571 alone or with As₂O₃ both could inhibit the proliferation of K562 cells. OD value in test groups reduced along with prolonging of action times, the OD values between different time points were significantly different (p < 0.05), furthermore the OD values at 72 hours in test groups were lowest, while as compared with control group, OD values at same time points in test groups all gradually decreased, among which decrease of OD value in test 5 group was most significant. The flow cytometric detection indicated that along with time prolonging, the apoptotic rate in control group not obviously changed, but the apoptotic rate in test groups gradually increased, the difference between time points was significant (p < 0.05), moreover apoptotic rate increased most obviously at 72 hours, while as compared with control group, apoptotic rate at same time points in test groups was gradually enhanced (p < 0.05), among which the apoptotic rate in test 5 group was highest. The real time qPCR assay revealed that as compared with control group, the bcl-xL mRNA expression in test groups reduced with decrease of 2-ΔΔCT value, furthermore the decrease of expression level in test 3 group was higher than that in test 2 group (p < 0.05), while the caspase 3 mRNA expression in test groups was enhanced with increase of 2-ΔΔCT value, moreover the increase of expression level in test 3 group was higher than that in test 2 group (p < 0.05). It is concluded that the STI571 can inhibit the proliferation of K562 cells, accelerate the apoptosis of K562 cells. The STI571 combined with As₂O₃ can enhance these two effects, increase the expression of caspase-3 mRNA and decrease the expression of bcl-xL mRNA. Therefore, the effect of STI571 combined with As₂O₃ on expression of caspase 3 and bcl-xL mRNA may be one of molecular mechanisms underlying their synergic antileukemia efficacy.