急性白血病患儿白血病干细胞表面CD96和CD71的表达对其疗效和预后的影响
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摘要
目的:观察白血病干细胞(LSC)表面CD96和CD71表达对急性白血病患儿疗效及预后的影响,阐明白血病患儿LSC的分子生物学特征与其疗效和预后的关联性。方法:选择80例急性白血病患儿作为研究对象,其中急性淋巴细胞白血病(ALL)39例,急性髓系白血病(AML)41例。应用流式细胞术对其LSC表面CD96和CD71表达情况进行检测,对患者的首次化疗疗效、5年生存率、化疗后感染、化疗后复发和髓外浸润发生率进行观察和比较。结果:38例(47.5%)患儿LSC表面CD96阳性表达,45例(56.3%)患儿LSC表面CD71阳性表达,2种抗原阳性表达率比较差异无统计学意义(χ~2=1.227,P=0.268);AML患儿LSC表面CD96和CD71阳性表达率均明显高于ALL患儿(χ~2=22.225,χ~2=34.028,均P<0.01)。LSC表面CD96阴性表达患儿首次化疗后的临床有效率和疗效分布均优于LSC表面CD96阳性表达患儿,LSC表面CD71阴性表达的患儿首次化疗后的临床有效率和疗效分布优于LSC表面CD71阳性表达患儿(χ~2=11.323,χ~2=16.589,P<0.05;U=2.939,U=2.291,P<0.05)。LSC表面CD96阴性表达患儿的5年生存率明显高于LSC表面CD96阳性表达患儿(χ~2=5.051,P<0.05),化疗后感染、化疗后复发和髓外浸润发生率明显低于LSC表面CD96阳性表达患儿(χ~2=8.316,χ~2=13.288,χ~2=5.389,均P<0.05);LSC表面CD71阴性表达患儿化疗后感染发生率和化疗后复发率明显低于LSC表面CD71阳性表达的患儿(χ~2=6.622,χ~2=10.787,均P<0.05)。结论:急性白血病患儿LSC表面的CD96和CD71表达水平与疾病亚型、首次化疗疗效具有一定的关联性,可作为辅助诊断和评价疗效的标志物;CD96的表达水平与患者的预后具有关联性,可作为预测患儿预后的指标。
Objective:To observe the influence of the CD96 and CD71 expressions in the surface of leukemia stem cells(LSC)in the therapeutic effects and prognosis of the children with acute leukemia,and to clarify the relationships between the molecular biological characteristics of LSC in the children with leukemia and their therapeutic effects and prognosis.Methods:Eighty children with acute leukemia were selected as the subjects.Among them,39 cases were acute lymphoblastic leukemia(ALL)and 41 cases were acute myeloid leukemia(AML).The CD96 and CD71 expressions on the surface of LSC were detected with flow cytometry;the therapeutic effects of the first cycle chemotherapy,the survival rate of 5-year,the incidence of infection after chemotherapy,the recurrence rate after chemotherapy,and the incidence of extramedullary infiltration of the children were observed and compared.Results:The CD96 expression on the surface of LSC was positive in 38 cases(47.5%)and the CD71 expression on the surface of LSC was positive in 45 cases(56.3%);the difference of positive expression rates of CD96 and CD71 was not significant(χ~2=1.227,P=0.268).The positive expression rates of CD96 and CD71 on the surface of LSC of the children with AML were significantly higher than those in the children with ALL,and the differences were statistically significant(χ~2=22.225,χ~2=34.028,P<0.01).The distribution of therapeutic effects and the clinical efficiency of the first cycle chemotherap,in the children with negative CD96 expression on the surface of LSC were superior to those with positive CD96 expression on the surface of LSC;the distribution of therapeutic effects and the clinical efficiency of the first cycle chemotherapy in the children with negative CD71 expression on the surface of LSC were superior than those with positive CD71 expression on the surface of LSC;the differences between two groups were statistically significant(χ~2=11.323,χ~2=16.589,P<0.05;U=2.939,U=2.291,P<0.05).The survival rate of 5-year in the children with negative CD96 expression on the surface of LSC was higher than those with positive CD96expression;the incidence of infection after chemotherapy,the recurrence rate after chemotherapy and the incidence of extramedullary infiltration were lower than those with positive CD96 expression.The incidence of infection after chemotherapy and the recurrence rate after chemotherapy in the children with negative CD71 expression on the surface of LSC were lower than those with positive CD71 expression,and the differences between two groups were statistically significant(χ~2=5.051,χ~2=13.288,P<0.05).Conclusion:The expressions of CD96 and CD71 on the surface of LSC in the children with acute leukemia has relationship with the subtypes of the disease and the therapeutic effects of the first cycle chemotherapy,which can be used as markers for the diagnosis and evaluation of therapeutic effects.The expression level of CD96 is related to the prognosis of the patients,which can be used as an indicator for predicting the prognosis of patients.
Objective:To observe the influence of the CD96 and CD71 expressions in the surface of leukemia stem cells(LSC)in the therapeutic effects and prognosis of the children with acute leukemia,and to clarify the relationships between the molecular biological characteristics of LSC in the children with leukemia and their therapeutic effects and prognosis.Methods:Eighty children with acute leukemia were selected as the subjects.Among them,39 cases were acute lymphoblastic leukemia(ALL)and 41 cases were acute myeloid leukemia(AML).The CD96 and CD71 expressions on the surface of LSC were detected with flow cytometry;the therapeutic effects of the first cycle chemotherapy,the survival rate of 5-year,the incidence of infection after chemotherapy,the recurrence rate after chemotherapy,and the incidence of extramedullary infiltration of the children were observed and compared.Results:The CD96 expression on the surface of LSC was positive in 38 cases(47.5%)and the CD71 expression on the surface of LSC was positive in 45 cases(56.3%);the difference of positive expression rates of CD96 and CD71 was not significant(χ~2=1.227,P=0.268).The positive expression rates of CD96 and CD71 on the surface of LSC of the children with AML were significantly higher than those in the children with ALL,and the differences were statistically significant(χ~2=22.225,χ~2=34.028,P<0.01).The distribution of therapeutic effects and the clinical efficiency of the first cycle chemotherap,in the children with negative CD96 expression on the surface of LSC were superior to those with positive CD96 expression on the surface of LSC;the distribution of therapeutic effects and the clinical efficiency of the first cycle chemotherapy in the children with negative CD71 expression on the surface of LSC were superior than those with positive CD71 expression on the surface of LSC;the differences between two groups were statistically significant(χ~2=11.323,χ~2=16.589,P<0.05;U=2.939,U=2.291,P<0.05).The survival rate of 5-year in the children with negative CD96 expression on the surface of LSC was higher than those with positive CD96expression;the incidence of infection after chemotherapy,the recurrence rate after chemotherapy and the incidence of extramedullary infiltration were lower than those with positive CD96 expression.The incidence of infection after chemotherapy and the recurrence rate after chemotherapy in the children with negative CD71 expression on the surface of LSC were lower than those with positive CD71 expression,and the differences between two groups were statistically significant(χ~2=5.051,χ~2=13.288,P<0.05).Conclusion:The expressions of CD96 and CD71 on the surface of LSC in the children with acute leukemia has relationship with the subtypes of the disease and the therapeutic effects of the first cycle chemotherapy,which can be used as markers for the diagnosis and evaluation of therapeutic effects.The expression level of CD96 is related to the prognosis of the patients,which can be used as an indicator for predicting the prognosis of patients.
引文
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[13]吴颖,肖敏,朱莉,等.91例急性白血病患者骨髓单个核细胞CD96分子的表达研究[J].中国实验血液学杂志,2011,19(3):585-588.
[14]肖平,曾耀英,林蔚.白血病干细胞相关抗原在急性白血病细胞中的表达[J].中华实用诊断与治疗杂志,2011,25(12):1179-1181.
[15]Ptoszyńska A,Ruckemann-Dziurdzińska K,Józwik A,et al.Cytometrie evaluation of transferring receptor l(CD71)in childhood acute lymphoblastic leukemia[J].Folia Histochem Cytobiol,2012,50(2):304-311.
[16]魏园玉,张晓飐,张帆,等.CD71作为增殖指标在血液肿瘤中的表达及与Ki-67的相关性分析[J].中国实验血液学杂志,2015,23(1):234-240.
[17]闫振宇,田旭,李莹,等.MDS与AA患者骨髓CD34+和CD71+CD45-细胞水平的变化[J].中国实验血液学杂志,2014,22(2):382-386.
[18]罗颖婉,佟红艳.骨髓增生异常综合征相关病因研究进展[J].中国实用内科杂志,2017,37(3):267-270.
[19]刘春燕.邵宗鸿.再生障碍性贫血发病机制研究进展[J].中国实用内科杂志,2016,36(5):345-349.
[20]江亚军,李秀梅,韩秀华,等.缺铁性贫血患者血清Hepcidin和红细胞CD71的变化[J].医学研究杂志,2013,42(8):126-129.
[2]Arora RS,Arora B.Acute leukemia in children:A review of the current Indian data[J].South Asian J Cancer,2016,5(3):155-160.
[3]Schoenaker MH,Suarez F,Szczepanski T,et al.Treatment of acute leukemia in children with ataxia telangiectasia(A-T)[J].Eur J Med Genet,2016,59(12):641-646.
[4]Ishii K,Barrett AJ.Novel immunotherapeutic approaches for the treatment of acute leukemia(myeloid and lymphoblastic)[J].Ther Adv Hematol,2016,7(1):17-39.
[5]邹东方,文飞球,于洁.急性白血病化疗对儿童认知功能影响评估的研究进展[J].中国实用儿科杂志,2015,30(10):791-795.
[6]景卉,冯茹.流式细胞术检测急性白血病微小残留病的研究进展[J].中国实验血液学杂志,2014,22(3):847-851.
[7]王荣华,陈信义,褚雨霆,等.白血病干细胞表面分子标志物及分化抗原高表达与难治性急性白血病[J].医学综述,2012,18(13):1973-1976.
[8]黄晖婷,彭琪,夏平方,等.靶向骨髓微环境治疗急性白血病的研究进展[J].国际输血及血液学杂志,2016,39(2):139-142.
[9]宋晓洁,冯伟平,韩雪娇,等.CD47在急性白血病干细胞中的表达及其对临床疗效及预后的影响[J].现代生物医学进展,2016,16(29):5760-5762,5796.
[10]王毅捷,孙和顺,马亚震.CD96及P选择素在急性白血病患者外周血中的表达及临床意义[J].血栓与止血学,2015,21(1):27-29,32.
[11]王学梅,严媚,刘玉,等.69例急性白血病患儿白血病干细胞CD96分子的表达及临床意义[J].中国当代儿科杂志,2013,15(8):633-637.
[12]刘晔华,陈锦艳,江雁,等.急性白血病患者骨髓干细胞CD_(96)、CD_(123)的表达及与预后的相关性[J].山东医药,2012,52(47):77-79.
[13]吴颖,肖敏,朱莉,等.91例急性白血病患者骨髓单个核细胞CD96分子的表达研究[J].中国实验血液学杂志,2011,19(3):585-588.
[14]肖平,曾耀英,林蔚.白血病干细胞相关抗原在急性白血病细胞中的表达[J].中华实用诊断与治疗杂志,2011,25(12):1179-1181.
[15]Ptoszyńska A,Ruckemann-Dziurdzińska K,Józwik A,et al.Cytometrie evaluation of transferring receptor l(CD71)in childhood acute lymphoblastic leukemia[J].Folia Histochem Cytobiol,2012,50(2):304-311.
[16]魏园玉,张晓飐,张帆,等.CD71作为增殖指标在血液肿瘤中的表达及与Ki-67的相关性分析[J].中国实验血液学杂志,2015,23(1):234-240.
[17]闫振宇,田旭,李莹,等.MDS与AA患者骨髓CD34+和CD71+CD45-细胞水平的变化[J].中国实验血液学杂志,2014,22(2):382-386.
[18]罗颖婉,佟红艳.骨髓增生异常综合征相关病因研究进展[J].中国实用内科杂志,2017,37(3):267-270.
[19]刘春燕.邵宗鸿.再生障碍性贫血发病机制研究进展[J].中国实用内科杂志,2016,36(5):345-349.
[20]江亚军,李秀梅,韩秀华,等.缺铁性贫血患者血清Hepcidin和红细胞CD71的变化[J].医学研究杂志,2013,42(8):126-129.