初治急性白血病患者骨髓细胞S期激酶相关蛋白和细胞周期抑制蛋白及细胞周期蛋白表达及意义

Expression of SKP2,P27 and cyclin proteins in patients with acute leukemia and its clinical significance

目的 探讨S期激酶相关蛋白（S phase kinase associated protein,SKP2）、细胞周期抑制蛋白（cell cycle inhibitor protein factor 27,P27）、细胞周期蛋白A1（cyclin A1）及细胞周期蛋白E（cyclin E）在急性白血病患者骨髓细胞中的表达及其意义。方法 57例急性白血病患者,其中22例初治急性非淋巴细胞白血病（acute non-lymphoid cell leukemia,ANLL）患者给予DA（柔红霉素＋阿糖胞苷）方案治疗,15例初治急性淋巴细胞性白血病（acute lymphatic leukemia,ALL）患者给予VDP（长春新碱＋柔红霉素＋泼尼松）方案治疗,10例复发ANLL患者给予MA方案（米托蒽琨＋阿糖胞苷）方案治疗,10例复发ALL患者给予VA（长春新碱＋阿糖胞苷）方案治疗;采用免疫组织化学法检测其骨髓细胞SKP2、P27、cyclin A1及cyclin E表达水平,并与20例非恶性血液肿瘤疾病患者（对照组）进行比较;分析急性白血病患者骨髓细胞SKP2、P27、cyclin A1及cyclin E表达阳性率与临床特征的相关性。结果 治疗3~4个疗程后,完全缓解9例（15.79%）,部分缓解41例（71.93%）,未缓解7例（12.28%）;完全缓解者SKP2[（19.83±5.62）%]、cyclin E[（8.21±6.22）%]及cyclin A1[（5.96±4.83）%]表达水平明显低于部分缓解＋未缓解者[（46.16±18.06）%、（41.19±12.16）%、（36.18±10.77）%]（P〈0.05）,P27表达水平[（26.04±7.08）%]明显高于部分缓解＋未缓解者[（15.36±4.98）%]（P〈0.05）;治疗前,初治ANLL、初治ALL、复发ANLL、复发ALL患者骨髓细胞SKP2[（44.76±23.81）%、（39.75±21.64）%、（46.53±24.18）%、（43.28±24.92）%]、cyclin E[（27.18±11.56）%、（33.49±12.74）%、（40.32±12.35）%、（37.08±10.96）%]及cyclin A1[（34.47±15.64）%、（32.08±14.93）%、（36.28±13.67）%、（33.94±14.25）%]表达水平均高于对照组[（15.64±4.96）%、（5.83±4.72）%、（7.54±6.49）%]（P〈0.05）;复发ANLL、复发ALL患者骨髓细胞P27[（16.09±6.32）%、（18.37±6.38）%]表达水平低于对照组[（27.95±6.83）%],并低于初治ANLL和初治ALL患者,差异均有统计学意义（P〈0.05）;初治急性白血病患者骨髓细胞SKP2、P27、cyclin E及cyclin A1阳性表达率在年龄、性别、乳酸脱氢酶水平上比较差异均无统计学意义（P〉0.05）;白细胞计数≥30×109/L者SKP2阳性表达率（85.00%）高于白细胞计数〈30×10~9/L者（47.06%）;经治疗完全缓解者SKP2阳性表达率（42.31%）低于部分缓解＋未缓解者（81.82%）,P27阳性表达率（69.23%）高于未缓解者（36.36%）,差异均有统计学意义（P〈0.05）。结论 急性白血病患者细胞周期调控因子SKP2、P27、cyclin E及cyclin A1在表达水平明显高于非恶性血液肿瘤疾病患者,SKP2、P27阳性表达与初治患者治疗效果有关。

Objective To investigate the expressions of S phase kinase associated protein （SKP2）, cell cycle inhibitor protein factor 27 （P27）, cyclin A1 and cyclin E in bone marrow cells of the patients with acute leukemia and its significance. Methods In 57 patients with acute leukemia, 22 patients with initially-treated acute non-lymphocytic leukemia （ANLL） received daunorubicin ＋ cytarabine （DA） regimen, 15 patients with initially-treated acute lymphoblastic leukemia （ALL） patients received daunorubicin＋vincristine＋prednisone （VDP） regimen, 10 patients with relapsed ANLL received mitoxantrone Kun ＋ cytarabine （MA） regimen, and 10 patients with relapsed ALL received arabinose cytidine （VA） regimen. The levels of SKP2, P27, cyclin A1 and cyclin E were detected and compared with another 20 patients with non-malignant hematological tumors （control group）. The correlations of the positive rates of SKP2, P27, cyclin A1 and cyclin E with the clinical features were analyzed. Results After 3 to 4 courses of treatment, the results were complete remission in 9 patients （15.79 % ）, partial remission in 41 patients （71.93 % ）, and no change in 7 patients （12.28%）. The levels of SKP2 （（19.83±5.62）%）, cyclin E （（8.21±6.22）%） and cyclin A1 （（5.96±4.83） %） in patients with complete remission were significantly lower than those in patients with partial remission and no change （（46.16±18.06） %, （41.19±12.16） %, （36.18±10.77） %） （P〈0.05）, and P27 level was significantly higherin patients with complete remission （（26.04±7.08）%） than that in patients with no change （（15.36：J：4.98）%） （P〈 0.05）. The levels of SKP2 （（44.76±23.81）%, （39.75±21.64）%, （46.53±24.18） %, （43.28±24.92）%）, cyelin E （（27.18±11.56）%, （33.49±12.74）%, （40.32±12.35）%, （37.08±10.96）%） and cyclin A1 （（34.47±15.64）%, （32.08 ± 14. 93）%, （36. 28± 13. 67）%, （33. 94±14. 25）%） in the patients with initially-treated ANLLL, initially-treated ALL, relapsed ANLL and relapsed ALL were significantly higher than those in control group （（15.64± 4. 961）%, （5.83±4.72）%, （7.54±6.49）%） before treatment （P〈0.05）. The level of P27 was significantly lower in patients with relapsed ANLL （（16.09 ±6.32） %） and relapsed ALL （（18.37 ±6. 38） %） than that in control group （（27.95±6.83） %）, and in initially-treated ANLL and ALL patients （P〈0.05）. There were no significant differences in positive rates of SKP2, P27, cyclin E and cyclin A1 among different age, gender and lactate dehydrogenase levels in initially-treated acute leukemia （P〈0.05）. The positive rate of SKP2 was significantly higher in patients with white blood cell count ≥30×109/L （85.00%） than that in patients with white blood cell count 〈30× 109/L （47.06%）, and lower in patients with complete remission （42. 31%） than that in patients with partial remission and no change （81.82%）. The positive rate of P27 was significantly higher in patients with complete remission （69.23%） than that in patients with no change （36. 36%） （P〈0. 05）. Conclusion The levels of SKP2, P27, cyclin E and cyclin A1 are significantly higher in patients with acute leukemia than those in patients with non-malignant hematologic tumors, and the positive expressions of P27 and SKP2 are correlated with the therapeutic effect in initially-treated patients.