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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 role of S phase kinase associated protein (SKP2), cell cycle inhibitor protein factor 27 (P27), cyclin A1 and cyclin E in Expression of bone marrow cells in patients with acute leukemia and its significance Methods Fifty-seven patients with acute leukemia, of which 22 patients with acute non-lymphoid cell leukemia (ANLL) were treated with DA (daunorubicin + cytarabine) regimen, 15 patients with initially treated acute lymph node Patients with acute lymphatic leukemia (ALL) were treated with VDP (vincristine + daunorubicin + prednisone) regimen and 10 patients with relapsed ANLL were treated with MA regimen (mitoxantrone + cytarabine) After treatment, 10 patients with relapsed ALL were treated with VA (vincristine + cytarabine) regimen; the expression levels of SKP2, P27, cyclin A1, and cyclin E in bone marrow cells were detected by immunohistochemistry and compared with 20 non-malignant blood samples. The patients with tumor diseases (control group) were compared; the positive rates of SKP2, P27, cyclin A1, and cyclin E expression in bone marrow cells of patients with acute leukemia were analyzed and correlated with clinical characteristics. Results After 3 to 4 courses of treatment, 9 cases (15.79%) were completely relieved, 41 cases (71.93%) partially relieved, and 7 cases (12.28%) were not relieved; SKP2 [(19.83±5.62)%] and cyclin were completely relieved. The expression levels of E [(8.21±6.22)%] and cyclin A1 [(5.96±4.83)%] were significantly lower than those of partial remission + non-remission [(46.16±18.06)%, (41.19±12.16)%, (36.18±10.77) )%] (P<0.05), P27 expression level [(26.04±7.08)%] was significantly higher than partial remission + nonremission [(15.36±4.98)%] (P<0.05); before treatment, the initial treatment of ANLL, Patients with ALL, relapsed ANLL, and relapsed ALL had bone marrow 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)%] and cyclin A1 [(34.47±15.64)%, (32.08±14.93)%, (36.28±13.67)%, ( The expression level of 33.94±14.25)% was higher than that of control group [(15.64±4.96)%, (5.83±4.72)%, (7.54±6.49)%] (P<0.05); bone marrow cells in relapsed ANLL and relapsed ALL patients The expression levels of [(16.09±6.32)%, (18.37±6.38)%] were lower than those in the control group [(27.95±6.83)%], and were lower than those of the newly diagnosed patients with ALL and primary ALL. The differences were statistically significant (P < 0.05). <0.05); The positive rates of SKP2, P27, cyclin E, and cyclin A1 in leukemia patients were not statistically different in terms of age, gender, and lactate dehydrogenase levels (P>0.05); SKP2 was greater than 30×109/L in white blood cell counts. The positive expression rate (85.00%) was higher than the white blood cell count <30×10~9/L (47.06%); the SKP2 positive expression rate (42.31%) was lower than the partial remission + non-remission (81.82%) The positive expression rate of P27 (69.23%) was higher than that of non-remission (36.36%). The difference was statistically significant (P<0.05). Conclusion The expression levels of cell cycle regulators SKP2, P27, cyclin E and cyclin A1 in patients with acute leukemia are significantly higher than those in non-malignant hematological malignancies. The positive expression of SKP2 and P27 is related to the treatment effect of newly diagnosed patients.