新基因HA117在儿童急性白血病中的表达及其临床意义
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摘要
目的检测新基因HA117在临床急性白血病患儿骨髓单个核细胞中的表达,并探讨其与多药耐药的关系。
方法应用RT-PCR方法检测36例不同时期急性白血病患儿骨髓单个核细胞HA117 DNA的表达情况;以10例特发性血小板减少性紫癜的患儿作为对照。
结果
①36例急性白血病患儿骨髓单个核细胞HA117 DNA阳性表达率为75.00%,急性淋巴细胞白血病组其阳性表达率(69.57%)与急性髓细胞白血病组(91.67%)比较无差异(χ~2=1.11,P>0.05)。但急性髓细胞白血病组HA117/β-actin半定量表达水平明显高于急性淋巴细胞白血病组(q=4.5852,P<0.01)。
②急性髓细胞白血病组和急性淋巴细胞白血病组HA117 DNA表达阳性率及HA117/β-actin半定量表达水平均高于对照组(χ~2=5.05,8.81;q=4.4612,6.9695,P<0.05)。
③初诊组患儿骨髓单个核细胞HA117 DNA阳性表达率(72.00℅)高于对照组(χ~2=5.91,P<0.05),与缓解组(81.82℅)比较没有明显差异(χ~2=0.01,P>0.05)。但其半定量表达水平明显高于缓解组和对照组(q=5.1991,6.3812 ,P<0.01)。
④缓解组HA117 DNA阳性表达率高于对照组(χ2=4.24 ,P<0.05),但其半定量水平与对照组比较无差异(q=1.6607,P>0.05)。
⑤未缓解组HA117/β-actin半定量水平高于缓解组和对照组(q=3.1705,4.4102;P<0.05),与初诊组比较无差异(q=0.5470,P>0.05)。
结论
①新基因HA117在初诊组和未缓解组临床儿童AL BMMNC中具有高表达;在缓解组HA117半定量表达和ITP对照组无差异。
②本实验提示临床以HA117半定量检测较其阳性表达检测更有意义。
③HA117基因水平变化,即在未缓解组和AML组高表达,在缓解组和ALL组低表达。推测HA117可能是影响临床缓解率的因素之一。
④前期实验结论结合本实验结果,在初诊组和未缓解组AL骨髓中,白血病细胞大量增殖,同时HA117基因在其两组中具有高表达;在缓解组AL骨髓中白血病细胞的增殖得到控制,HA117基因此时成低表达。说明新基因HA117表达于肿瘤组织。其可能参与了白血病的多药耐药,是导致AL细胞对化疗药物不敏感的原因之一。
Objective To explore the correlation between the expression of HA117 gene in bone marrow mononuclear cells and its relationship with multidrug resistance.
Methods HA117 gene expression in 36 acute leukemia patients, and 10 ITP patients controls were studied using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique.
Results
①The positive expression rate of HA117 gene in the patients was 75.00%. There was no significant difference in HA117 gene expression between ALL cells (69.57%) and AML cells (91.67%), but HA117/β-actin Semi-quantitative expression levels in AML were higher than that in ALL(q=4.5852,P<0.01).
②HA117 gene expression and HA117/β-actin Semi-quantitative expression levels in ALL and AML were higher than that in ITP patients (χ~2 =5.05,8.81;q=4.4612,6.9695;P<0.05).
③HA117 gene expression in initially treated patients were higher than that in ITP patients(χ~2=5.91,P<0.05),there was no significant difference form remission patients (χ~2=0.01,P>0.05),but HA117/β-actin Semi-quantitative expression levels in initially treated patients higher than remission patients and ITP patients(q=5.1991,6.3812,P<0.01).
④HA117 gene expression in remission patients were higher than that in ITP patients(χ~2=4.24,P<0.05), but there was no significant difference in HA117/β-actin Semi-quantitative expression levels from ITP patients(q=1.6607,P>0.05).
⑤HA117/β-actin Semi-quantitative expression levels in non- remission patients were higher than that in remission patients and ITP patients (q=3.1705,4.4102,P<0.05), but there was no significant difference from initially treated patients(q=0.5470,P>0.05).
Conclusion
①New gene HA117 was high expression in initially treated and non- remission patients in the BMMNC of children with AL, semi-quantitative expression of HA117 in remission patients was no difference between patients with ITP.
②The experiments show that clinical testing of its quantitative expression levels was more meaningful.
③HA117 gene level changed, Non-remission and AML group were high expression, ALL and remission group were low expression. HA117 was one of the factors which may affect the clinical remission rate.
④Conclusions in light of the early experimental results combined with the experimental results, in the BMMNC of initially treated and non- remission patients, the leukemia cells proliferation were rapidly, while HA117 gene in the two groups was high expression; In remission group, leukemia cells proliferation was controlled, while HA117 gene was low expression. HA117 new gene expressed in tumor tissue, it may be involved in multidrug resistance of leukemia. HA117 may be one of the reasons which AL cells was not sensitive to chemotherapeutic drugs.
方法应用RT-PCR方法检测36例不同时期急性白血病患儿骨髓单个核细胞HA117 DNA的表达情况;以10例特发性血小板减少性紫癜的患儿作为对照。
结果
①36例急性白血病患儿骨髓单个核细胞HA117 DNA阳性表达率为75.00%,急性淋巴细胞白血病组其阳性表达率(69.57%)与急性髓细胞白血病组(91.67%)比较无差异(χ~2=1.11,P>0.05)。但急性髓细胞白血病组HA117/β-actin半定量表达水平明显高于急性淋巴细胞白血病组(q=4.5852,P<0.01)。
②急性髓细胞白血病组和急性淋巴细胞白血病组HA117 DNA表达阳性率及HA117/β-actin半定量表达水平均高于对照组(χ~2=5.05,8.81;q=4.4612,6.9695,P<0.05)。
③初诊组患儿骨髓单个核细胞HA117 DNA阳性表达率(72.00℅)高于对照组(χ~2=5.91,P<0.05),与缓解组(81.82℅)比较没有明显差异(χ~2=0.01,P>0.05)。但其半定量表达水平明显高于缓解组和对照组(q=5.1991,6.3812 ,P<0.01)。
④缓解组HA117 DNA阳性表达率高于对照组(χ2=4.24 ,P<0.05),但其半定量水平与对照组比较无差异(q=1.6607,P>0.05)。
⑤未缓解组HA117/β-actin半定量水平高于缓解组和对照组(q=3.1705,4.4102;P<0.05),与初诊组比较无差异(q=0.5470,P>0.05)。
结论
①新基因HA117在初诊组和未缓解组临床儿童AL BMMNC中具有高表达;在缓解组HA117半定量表达和ITP对照组无差异。
②本实验提示临床以HA117半定量检测较其阳性表达检测更有意义。
③HA117基因水平变化,即在未缓解组和AML组高表达,在缓解组和ALL组低表达。推测HA117可能是影响临床缓解率的因素之一。
④前期实验结论结合本实验结果,在初诊组和未缓解组AL骨髓中,白血病细胞大量增殖,同时HA117基因在其两组中具有高表达;在缓解组AL骨髓中白血病细胞的增殖得到控制,HA117基因此时成低表达。说明新基因HA117表达于肿瘤组织。其可能参与了白血病的多药耐药,是导致AL细胞对化疗药物不敏感的原因之一。
Objective To explore the correlation between the expression of HA117 gene in bone marrow mononuclear cells and its relationship with multidrug resistance.
Methods HA117 gene expression in 36 acute leukemia patients, and 10 ITP patients controls were studied using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique.
Results
①The positive expression rate of HA117 gene in the patients was 75.00%. There was no significant difference in HA117 gene expression between ALL cells (69.57%) and AML cells (91.67%), but HA117/β-actin Semi-quantitative expression levels in AML were higher than that in ALL(q=4.5852,P<0.01).
②HA117 gene expression and HA117/β-actin Semi-quantitative expression levels in ALL and AML were higher than that in ITP patients (χ~2 =5.05,8.81;q=4.4612,6.9695;P<0.05).
③HA117 gene expression in initially treated patients were higher than that in ITP patients(χ~2=5.91,P<0.05),there was no significant difference form remission patients (χ~2=0.01,P>0.05),but HA117/β-actin Semi-quantitative expression levels in initially treated patients higher than remission patients and ITP patients(q=5.1991,6.3812,P<0.01).
④HA117 gene expression in remission patients were higher than that in ITP patients(χ~2=4.24,P<0.05), but there was no significant difference in HA117/β-actin Semi-quantitative expression levels from ITP patients(q=1.6607,P>0.05).
⑤HA117/β-actin Semi-quantitative expression levels in non- remission patients were higher than that in remission patients and ITP patients (q=3.1705,4.4102,P<0.05), but there was no significant difference from initially treated patients(q=0.5470,P>0.05).
Conclusion
①New gene HA117 was high expression in initially treated and non- remission patients in the BMMNC of children with AL, semi-quantitative expression of HA117 in remission patients was no difference between patients with ITP.
②The experiments show that clinical testing of its quantitative expression levels was more meaningful.
③HA117 gene level changed, Non-remission and AML group were high expression, ALL and remission group were low expression. HA117 was one of the factors which may affect the clinical remission rate.
④Conclusions in light of the early experimental results combined with the experimental results, in the BMMNC of initially treated and non- remission patients, the leukemia cells proliferation were rapidly, while HA117 gene in the two groups was high expression; In remission group, leukemia cells proliferation was controlled, while HA117 gene was low expression. HA117 new gene expressed in tumor tissue, it may be involved in multidrug resistance of leukemia. HA117 may be one of the reasons which AL cells was not sensitive to chemotherapeutic drugs.
引文
[1]王吉耀主编.内科学[M],北京:人民卫生出版社,2005,745-762.
[2]吴玥.儿童急性髓细胞白血病诊治进展[A].2007年全国小儿血液与肿瘤学术会议专题讲座[C];2007:1-11.
[3]顾龙君.儿童急性淋巴细胞白血病诊治的回顾与进展[A].2007年全国小儿血液与肿瘤学术会议专题讲座[C];2007:11-22.
[4]郑胡镛.开展肿瘤综合治疗,提高康复儿童生活质量[A].2007年全国小儿血液与肿瘤学术会议专题讲座[C];2007:22-23.
[5]文川,万伍卿.儿童白血病的化疗决策[J].医学与社会,2006,19(7):30-31.
[6]郭玉霞,罗庆,徐酉华.耐药相关新基因HA117的克隆及重组腺病毒制备[J] .重庆医科大学学报,2008,33(6):641-644.
[7]程坚,陈宝安.白血病多药耐药相关基因临床研究新进展[J].东方大学学报(医学版),2007,26(3):225-229.
[8] Nadali F,Pourfathollah AA,Alimoghaddam K,et a1.Multidrug resistance inhibition by antisense oligonucleotide against MDR1/mRNA in P-glycoprotein expressing leukemic cells. [J].Hematology. 2007,12(5):393-401.
[9] Fedasenka UU, Shman TV, Savitski VP,et a1.Expression of MDR1, LRP, BCRP and Bcl-2 genes at diagnosis of childhood all: comparison with MRD status after induction therapy[J]. Exp Oncol,2008 ,30(3):248-252.
[10] van den Heuvel-Eibrink MM, van der Holt B, Burnett AK et a1.CD34-related co expression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age[J].Ann Hematol,2007,86(5):329-337.
[11] Pennati M, Folini M, Zaffaroni N. Targeting surviving in cancer therapy: fulfilled promises and open questions. Carcinogenesis. 2007,28(6):1133-1139.
[12] ABD EL-GHAFFAR H A,ALADLE D A,FARAHAT S E,et al.P- glycoprotein(p-170) expression in acute leukemias[J].Hematology,2006,11(1):35-41.
[13] HEE J H,CHAN-JEOUNG P,SEONGSOO J,et al. Prognostic significance of multidrugresistance genel(MDRI),multidrug resistance-related protein(MRP) and lung resistance Protein (LRP) mRNA expression in acute leukemia[J].J Korean Med Sci,2006,21:253-258.
[14] SUAREZ L,VIDRIALES M B,GARCIA-LARANA J,et al.CD34+ cells form acute myeloid leukemia,myelodysplastic syndromes, and normal bone marrow display different apoptosis and drug resistance- associated phenotypes[ J].Clin Cancer Res,2004,10(22):7599-7606.
[15] GAlMBERTI S,GUERRINI F,CARULLI G. significant co-ex-Passion of WTl and MDR1 genes in acute myeloid leukemia patients at diagllosis[ J].Eur J Haematol,2004, 72(1):45-51.
[16] BENDERRA Z,FAUSSAT A M,SAYADA L,et al. Boast cancer resistance protein and P-glycol protein in l49 adult acute myeloid leukemia[J].Clin Cance Reas ,2004,10(23):7896-7902.
[17] BENDERRA Z,FAUSSAT A M,SAYADA L,et al.MRP3,BCRP,and p-glycoprotein activities are prognostic factors in adult acute myeloid leukemia[J].Clin Cancer Res,2005,11(21):7764-772.
[18] SWERTS K,de MOERLOOSEB,DHOOGE C,et al. prognostic significance of multidrug resistance-related proteins in childhood acute lymphoblastic leukemia[J].Eur J Cancer,2006,42 (3):295-309.
[19] PLASSCHAERT S L,de BONT E S,BOEZEN M,et al. Expression of multidrug resistance- associated proteins Predicts prognosis in childhood and adult acute lymphoblastic leukemia[J].Clin Cacner Res,2005,11(24):8661- 8668.
[20] VALERA E T,SCRIDELI C A,QUEIROZ R G,et al. Multiple Dr resistance Protein(MDR-1) , multidrug resistance-elated protein(MRP) and lung resistance protein(LRP) gene expression in childhood acute lymphoblastic Leukemia[J].Sao Palou Med J,2004,122(4):166-171.
[21] GURBUXANI S,SINGH A L,RAINA V,et al. Significance of MDR1,MRP1,GSTPi and GSTmu mRNA expression in acute lymphoblastic leukemia in Indian Patients[J].Cancer Lett,2001,167(1):73-83.
[1]高举,陆晓茜.儿童特发性再生障碍性贫血的诊断与治疗[J].临床儿科杂,2007,25(8):716-720
[2]吴天姊,姜振宇.生障碍性贫血综述[J].中国临床医药研究杂志,2006,154:58-59
[3]谢晓恬,应大明执笔.小儿再生障碍性贫血诊疗建议[J].中国小儿血液与肿瘤杂志,2007,12(5):236-240
[4] Brodsky RA, Jones RJ.Aplastic anemia[J].Lancet,2005,365(9471):1647—1656
[5]陈静,王茜,施英唐,等.再生障碍性贫血患儿骨髓间充质干细胞的生物学特点[J].中国实验血液学杂志,2005,13(5):832—838
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[12]中华医学会第四届全国再生障碍性贫血学术会议纪要.再生障碍性贫血诊断标准.中华血液学杂志,1987,8:486
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[14]陈纯.再生障碍性贫血的临床诊断治疗进展[J].实用儿科临床杂志,2007,22(15):1123-1126
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[16] Marsh JC,Ball SE,Darhyshire P,et a1.Guidelines for the diagnosis and management of acquired aplastic anaemia[J].Br J Haematol,2003,123(5):782—801.
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[18] Goldenberg NA,Graham DK,Lian g X,et a1.Successful treatment of severe aplastic anemia in children using standardized irmnunosuppreasive thempy with antithymocyte globulin cyclosporine A[J].Pediatr Blood Can cer,2OO4,43:718-722.
[19] Dads JK,Guinan EC.An update on the management of severe idiopathic aplastic anemia in children[J].Br J Heraatol,2007,136(4):549—564
[2]吴玥.儿童急性髓细胞白血病诊治进展[A].2007年全国小儿血液与肿瘤学术会议专题讲座[C];2007:1-11.
[3]顾龙君.儿童急性淋巴细胞白血病诊治的回顾与进展[A].2007年全国小儿血液与肿瘤学术会议专题讲座[C];2007:11-22.
[4]郑胡镛.开展肿瘤综合治疗,提高康复儿童生活质量[A].2007年全国小儿血液与肿瘤学术会议专题讲座[C];2007:22-23.
[5]文川,万伍卿.儿童白血病的化疗决策[J].医学与社会,2006,19(7):30-31.
[6]郭玉霞,罗庆,徐酉华.耐药相关新基因HA117的克隆及重组腺病毒制备[J] .重庆医科大学学报,2008,33(6):641-644.
[7]程坚,陈宝安.白血病多药耐药相关基因临床研究新进展[J].东方大学学报(医学版),2007,26(3):225-229.
[8] Nadali F,Pourfathollah AA,Alimoghaddam K,et a1.Multidrug resistance inhibition by antisense oligonucleotide against MDR1/mRNA in P-glycoprotein expressing leukemic cells. [J].Hematology. 2007,12(5):393-401.
[9] Fedasenka UU, Shman TV, Savitski VP,et a1.Expression of MDR1, LRP, BCRP and Bcl-2 genes at diagnosis of childhood all: comparison with MRD status after induction therapy[J]. Exp Oncol,2008 ,30(3):248-252.
[10] van den Heuvel-Eibrink MM, van der Holt B, Burnett AK et a1.CD34-related co expression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age[J].Ann Hematol,2007,86(5):329-337.
[11] Pennati M, Folini M, Zaffaroni N. Targeting surviving in cancer therapy: fulfilled promises and open questions. Carcinogenesis. 2007,28(6):1133-1139.
[12] ABD EL-GHAFFAR H A,ALADLE D A,FARAHAT S E,et al.P- glycoprotein(p-170) expression in acute leukemias[J].Hematology,2006,11(1):35-41.
[13] HEE J H,CHAN-JEOUNG P,SEONGSOO J,et al. Prognostic significance of multidrugresistance genel(MDRI),multidrug resistance-related protein(MRP) and lung resistance Protein (LRP) mRNA expression in acute leukemia[J].J Korean Med Sci,2006,21:253-258.
[14] SUAREZ L,VIDRIALES M B,GARCIA-LARANA J,et al.CD34+ cells form acute myeloid leukemia,myelodysplastic syndromes, and normal bone marrow display different apoptosis and drug resistance- associated phenotypes[ J].Clin Cancer Res,2004,10(22):7599-7606.
[15] GAlMBERTI S,GUERRINI F,CARULLI G. significant co-ex-Passion of WTl and MDR1 genes in acute myeloid leukemia patients at diagllosis[ J].Eur J Haematol,2004, 72(1):45-51.
[16] BENDERRA Z,FAUSSAT A M,SAYADA L,et al. Boast cancer resistance protein and P-glycol protein in l49 adult acute myeloid leukemia[J].Clin Cance Reas ,2004,10(23):7896-7902.
[17] BENDERRA Z,FAUSSAT A M,SAYADA L,et al.MRP3,BCRP,and p-glycoprotein activities are prognostic factors in adult acute myeloid leukemia[J].Clin Cancer Res,2005,11(21):7764-772.
[18] SWERTS K,de MOERLOOSEB,DHOOGE C,et al. prognostic significance of multidrug resistance-related proteins in childhood acute lymphoblastic leukemia[J].Eur J Cancer,2006,42 (3):295-309.
[19] PLASSCHAERT S L,de BONT E S,BOEZEN M,et al. Expression of multidrug resistance- associated proteins Predicts prognosis in childhood and adult acute lymphoblastic leukemia[J].Clin Cacner Res,2005,11(24):8661- 8668.
[20] VALERA E T,SCRIDELI C A,QUEIROZ R G,et al. Multiple Dr resistance Protein(MDR-1) , multidrug resistance-elated protein(MRP) and lung resistance protein(LRP) gene expression in childhood acute lymphoblastic Leukemia[J].Sao Palou Med J,2004,122(4):166-171.
[21] GURBUXANI S,SINGH A L,RAINA V,et al. Significance of MDR1,MRP1,GSTPi and GSTmu mRNA expression in acute lymphoblastic leukemia in Indian Patients[J].Cancer Lett,2001,167(1):73-83.
[1]高举,陆晓茜.儿童特发性再生障碍性贫血的诊断与治疗[J].临床儿科杂,2007,25(8):716-720
[2]吴天姊,姜振宇.生障碍性贫血综述[J].中国临床医药研究杂志,2006,154:58-59
[3]谢晓恬,应大明执笔.小儿再生障碍性贫血诊疗建议[J].中国小儿血液与肿瘤杂志,2007,12(5):236-240
[4] Brodsky RA, Jones RJ.Aplastic anemia[J].Lancet,2005,365(9471):1647—1656
[5]陈静,王茜,施英唐,等.再生障碍性贫血患儿骨髓间充质干细胞的生物学特点[J].中国实验血液学杂志,2005,13(5):832—838
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