成人急性白血病患者白细胞和血小板中活性氧簇的监测研究
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摘要
目的 :检测成人急性白血病患者外周血白细胞和血小板中活性氧簇(reactive oxygen species,ROS)阳性表达的水平及其在治疗前、后的变化,探讨白细胞和血小板中ROS水平的差异及其与疾病转归间的相关性。方法:选取16例成人急性白血病患者和16名健康对照者(健康对照组),16例患者按白血病分型分为急性淋巴细胞白血病组和急性髓细胞白血病组,分别观察治疗前和治疗后外周血白细胞和血小板中ROS的情况。采用流式细胞术检测外周血中白细胞和血小板中ROS阳性的表达水平,并用表达ROS阳性细胞的百分比来反映细胞内的ROS水平。结果:急性白血病患者治疗前、后外周血白细胞及血小板中的ROS水平均明显高于健康对照组(P<0.01);且患者治疗前外周血白细胞及血小板中的ROS水平显著高于治疗后(P<0.01)。急性白血病患者治疗前白细胞与血小板内的ROS水平存在正相关关系(r=0.535,P<0.05),健康对照组和急性白血病患者治疗后外周血白细胞与同组血小板内的ROS水平间不存在相关性。所有患者白细胞中白血病细胞所占百分比与ROS阳性表达间不存在相关性。急性白血病患者治疗前白细胞内的ROS水平明显高于同一患者血小板内的ROS水平(P<0.01)。急性淋巴细胞白血病患者与急性髓细胞白血病患者外周血白细胞、血小板中表达ROS阳性的百分比差异无统计学意义。结论:动态监测急性白血病患者外周血白细胞及血小板中ROS阳性的百分比对治疗疗效和预后判断有一定参考意义。
Objective: To study the level of reactive oxygen species(ROS) in leukocytes and platelets of peripheral blood from patients with leukemia before and after treatment, and study the difference in ROS level between leukocytes and platelets and their relationship with the outcome of leukemia. Methods: Sixteen adult patients with acute leukemia were enrolled and 16 healthy volunteers were served as controls. Patients were divided into ALL and AML groups, and were studied both before and after treatment. ROS was detected with flow cytometry and the percentage of ROS-positive cells was used to reflect the intracellular ROS level. Results: The percentages of ROS-positive leukocytes and platelets in patients with acute leukemia before and after treatment were both significantly higher than those in control group(P<0.01);the percentages of ROS-positive leukocytes and platelets before treatment were significantly higher than that after treat-ment(P<0.01). The percentage of ROS-positive cells in leukocytes was correlated with that in platelets before treatment(r=0.535, P<0.05). The ROS level of leukocytes was always higher than that of platelets in the same patients before treat-ment(P<0.01). There was no significant difference between AML patients and ALL patients in percentages of ROS-positive leukocytes and platelets. Conclusions: Dynamically monitoring the ROS level in peripheral leukocytes and platelets is helpful for the evaluation of treatment and prediction of prognosis in acute leukemia.
Objective: To study the level of reactive oxygen species(ROS) in leukocytes and platelets of peripheral blood from patients with leukemia before and after treatment, and study the difference in ROS level between leukocytes and platelets and their relationship with the outcome of leukemia. Methods: Sixteen adult patients with acute leukemia were enrolled and 16 healthy volunteers were served as controls. Patients were divided into ALL and AML groups, and were studied both before and after treatment. ROS was detected with flow cytometry and the percentage of ROS-positive cells was used to reflect the intracellular ROS level. Results: The percentages of ROS-positive leukocytes and platelets in patients with acute leukemia before and after treatment were both significantly higher than those in control group(P<0.01);the percentages of ROS-positive leukocytes and platelets before treatment were significantly higher than that after treat-ment(P<0.01). The percentage of ROS-positive cells in leukocytes was correlated with that in platelets before treatment(r=0.535, P<0.05). The ROS level of leukocytes was always higher than that of platelets in the same patients before treat-ment(P<0.01). There was no significant difference between AML patients and ALL patients in percentages of ROS-positive leukocytes and platelets. Conclusions: Dynamically monitoring the ROS level in peripheral leukocytes and platelets is helpful for the evaluation of treatment and prediction of prognosis in acute leukemia.
引文
[1]Rothe G,Valet G.Flow cytometric analysis of respiratory burst activity in phagocytes with hydroethidine and 2',7'-dichlorofluorescin[J].J Leukoc Biol,1990,47(5):440-448.
[2]蔡辉,姜丽娜,李柏青.流式细胞术检测中性粒细胞产生活性氧方法学探讨[J].蚌埠医学院学报,2010,35(6):541-547.
[3]Valko M,Leibfritz D,Moncol J,et al.Free radicals and antioxidants in normal physiological functions and human disease[J].Int J Biochem Cell Biol,2007,39(1):44-84.
[4]Hole PS,Darley RL,Tonks A.Do reactive oxygen species play a role in myeloid leukemias?[J].Blood,2011,117(22):5816-5826.
[5]Ahmad R,Tripathi AK,Tripathi P,et al.Studies on lipid peroxidation and non-enzymatic antioxidant status as indices of oxidative stress in patients with chronic myeloid leukaemia[J].Singapore Med J,2010,51(2):110-115.
[6]Zhou FL,Zhang WG,Wei YC,et al.Involvement of oxidative stress in the relapse of acute myeloid leukemia[J].J Biol Chem,2010,285(20):15010-15015.
[7]Devi GS,Prasad MH,Saraswathi I,et al.Free radicals antioxidant enzymes and lipid peroxidation in different types of leukemias[J].Clin Chim Acta,2000,293(1-2):53-62.
[8]Freedman JE.Oxidative stress and platelets[J].Arterioscler Thromb Vasc Biol,2008,28(3):s11-s16.
[9]Stokes KY,Russell JM,Jennings MH,et al.Platelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype induced by hypercholesterolemia[J].Free Radic Biol Med,2007,43(1):22-30.
[10]Raghuvanshi R,Chandra M,Misra PC,et al.Effect of vitamin E on the platelet xanthine oxidase and lipid peroxidation in the patients of myocardial infarction[J].Indian J Clin Biochem,2005,20(1):26-29.
[11]Imbach P.Oxidative stress may cause ITP[J].Blood,2011,117(17):4405-4406.
[12]Nicco C,Laurent A,Chereau C,et al.Differential modulation of normal and tumor cell proliferation by reactive oxygen species[J].Biomed Pharmacother,2005,59(4):169-174.
[13]Ozben T.Oxidative stress and apoptosis:impact on cancer therapy[J].J Pharm Sci,2007,96(9):2181-2196.
[14]Baǐgriaik E,Uslu K,Yurtu E,et al.Stobadine inhibits doxorubicin-induced apoptosis through a caspase-9 dependent pathway in P815 mastocytoma cells[J].Cell Biol Int,2007,31(9):979-984.
[15]Savatier J,Rharass T,Canal C,et al.Adriamycin dose and time effects on cell cycle,cell death,and reactive oxygen species generation in leukaemia cells[J].Leuk Res,2012,36(6):791-798.
[16]Miller WH Jr.Motlecular targets of arsenic trioxide in malignantcells[J].Oncologist,2002,7(Suppl 1):14-19.
[17]Jeanne M,Lallemand-Breitenbach V,Ferhi O,et al.PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3[J].Cancer Cell,2010,18(1):88-98.
[18]Doudican NA,Bowling B,Orlow SJ.Enhancement of arsenic trioxide cytotoxicity by dietary isothiocyanates in human leukemic cells via a reactive oxygen speciesdependent mechanism[J].Leuk Res,2010,34(2):229-234.
[19]Pei S,Minhajuddin M,Callahan KP,et al.Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells[J].J Biol Chem,2013,288(47):33542-33558.
[20]贺钰磊,曹励之,杨静,等.急性淋巴细胞白血病患儿WAVE1和p22phox的表达及WAVE1与氧化应激的关系[J].中国当代儿科杂志,2009,11(2):88-92.
[21]El-Sabagh ME,Ramadan KS,El-slam IMA,et al.Antioxidants status in acute lymphoblastic leukemic patients[J].Am J Med Med Sci,2011,1(1):1-6.
[2]蔡辉,姜丽娜,李柏青.流式细胞术检测中性粒细胞产生活性氧方法学探讨[J].蚌埠医学院学报,2010,35(6):541-547.
[3]Valko M,Leibfritz D,Moncol J,et al.Free radicals and antioxidants in normal physiological functions and human disease[J].Int J Biochem Cell Biol,2007,39(1):44-84.
[4]Hole PS,Darley RL,Tonks A.Do reactive oxygen species play a role in myeloid leukemias?[J].Blood,2011,117(22):5816-5826.
[5]Ahmad R,Tripathi AK,Tripathi P,et al.Studies on lipid peroxidation and non-enzymatic antioxidant status as indices of oxidative stress in patients with chronic myeloid leukaemia[J].Singapore Med J,2010,51(2):110-115.
[6]Zhou FL,Zhang WG,Wei YC,et al.Involvement of oxidative stress in the relapse of acute myeloid leukemia[J].J Biol Chem,2010,285(20):15010-15015.
[7]Devi GS,Prasad MH,Saraswathi I,et al.Free radicals antioxidant enzymes and lipid peroxidation in different types of leukemias[J].Clin Chim Acta,2000,293(1-2):53-62.
[8]Freedman JE.Oxidative stress and platelets[J].Arterioscler Thromb Vasc Biol,2008,28(3):s11-s16.
[9]Stokes KY,Russell JM,Jennings MH,et al.Platelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype induced by hypercholesterolemia[J].Free Radic Biol Med,2007,43(1):22-30.
[10]Raghuvanshi R,Chandra M,Misra PC,et al.Effect of vitamin E on the platelet xanthine oxidase and lipid peroxidation in the patients of myocardial infarction[J].Indian J Clin Biochem,2005,20(1):26-29.
[11]Imbach P.Oxidative stress may cause ITP[J].Blood,2011,117(17):4405-4406.
[12]Nicco C,Laurent A,Chereau C,et al.Differential modulation of normal and tumor cell proliferation by reactive oxygen species[J].Biomed Pharmacother,2005,59(4):169-174.
[13]Ozben T.Oxidative stress and apoptosis:impact on cancer therapy[J].J Pharm Sci,2007,96(9):2181-2196.
[14]Baǐgriaik E,Uslu K,Yurtu E,et al.Stobadine inhibits doxorubicin-induced apoptosis through a caspase-9 dependent pathway in P815 mastocytoma cells[J].Cell Biol Int,2007,31(9):979-984.
[15]Savatier J,Rharass T,Canal C,et al.Adriamycin dose and time effects on cell cycle,cell death,and reactive oxygen species generation in leukaemia cells[J].Leuk Res,2012,36(6):791-798.
[16]Miller WH Jr.Motlecular targets of arsenic trioxide in malignantcells[J].Oncologist,2002,7(Suppl 1):14-19.
[17]Jeanne M,Lallemand-Breitenbach V,Ferhi O,et al.PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3[J].Cancer Cell,2010,18(1):88-98.
[18]Doudican NA,Bowling B,Orlow SJ.Enhancement of arsenic trioxide cytotoxicity by dietary isothiocyanates in human leukemic cells via a reactive oxygen speciesdependent mechanism[J].Leuk Res,2010,34(2):229-234.
[19]Pei S,Minhajuddin M,Callahan KP,et al.Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells[J].J Biol Chem,2013,288(47):33542-33558.
[20]贺钰磊,曹励之,杨静,等.急性淋巴细胞白血病患儿WAVE1和p22phox的表达及WAVE1与氧化应激的关系[J].中国当代儿科杂志,2009,11(2):88-92.
[21]El-Sabagh ME,Ramadan KS,El-slam IMA,et al.Antioxidants status in acute lymphoblastic leukemic patients[J].Am J Med Med Sci,2011,1(1):1-6.