儿童急性白血病的实验、临床及循证医学研究
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摘要
目的：由于原代白血病细胞与体内白血病细胞的生物学性状相似,且遗传性状稳定,但原代细胞的培养存在培养条件要求高、细胞存活率低等缺点。为此,本文就儿童原代白血病细胞的分离及最优化的培养方法进行研究,为儿童急性白血病(AL)的体外研究提供细胞模型。
方法：选取2008年8月-2009年9月本院儿科收治的25例初诊AL患儿作为研究对象。于治疗前抽取肝素抗凝的骨髓液或外周血2-3 ml于无菌离心管中,利用人淋巴细胞分离液即可分离出白血病细胞。在倒置光学显微镜下观察不同时间点的原代白血病细胞的形态变化,以及利用CCK-8法检测不同细胞密度、不同成分的培养液对原代白血病细胞增殖活性的影响。
结果：细胞形态学观察及细胞增殖活力测定提示：原代白血病细胞在72 h以内存活率较高；高密度细胞[(4-10)×106/ml]培养低于密度细胞[(1-2)×106/ml]；胎牛血清较患儿自身的血清更有利于原代白血病细胞生长。
结论：利用人淋巴细胞分离液可以成功地分离出原代白血病细胞,而对于原代白血病细胞的体外培养,选择(4-6)×106/ml细胞密度接种于含10%胎牛血清的培养基中生长效果最理想。
目的：探讨小檗碱诱导儿童原代白血病细胞增殖、凋亡的作用。
方法：取初诊的22例白血病患儿的骨髓或外周血2-3 ml,用人淋巴细胞分离液分离出原代白血病细胞。将其分为：(1)对照组；(2)25 uM小檗碱；(3)50uM小檗碱；(4)100uM小檗碱。于24、48、72h时,利用CCK-8法检测小檗碱对每组原代白血病细胞的生长抑制率；同时24 h采用流式细胞术PI染色法及倒置显微镜观察不同浓度小檗碱诱导原代白血病细胞凋亡的影响。
结果：不同浓度(25、50、100 uM)的小檗碱作用于原代白血病细胞24、48、72h后,CCK-8法检测的每组细胞生长抑制率有明显差异(F=125.86,12.67 P均<0.01)。利用光学显微镜观察：细胞作用24 h已发生典型的凋亡变化。流式细胞术PI染色结果提示25、50、100 uM小檗碱作用原代细胞24 h后,其凋亡率分别为28.51%、31.98%、48.60%。
结论：小檗碱具有诱导儿童原代白血病细胞凋亡并抑制细胞增殖的作用,且呈剂量、时间依赖性。
目的：探讨儿童急性白血病细胞MDM2、P53基因表达及其与小檗碱对白血病原代细胞生长抑制的关系。
方法：选取本院儿科收治的40例初诊AL患儿作为研究对象,利用人淋巴细胞分离液分离出原代白血病细胞,并用CCK-8法检测不同浓度小檗碱作用原代白血病细胞24 h的细胞生长抑制率。RT-PCR法和免疫组织化学法检测MDM2、P53在白血病细胞中的表达,并比较MDM2、P53mRNA的表达与小檗碱对原代白血病细胞生长抑制的关系。
结果：儿童白血病中存在MDM2、P53的表达,其中MDM2、P53蛋白阳性率分别为66.67%、22.78%,而MDM2、P53mRNA的表达率分别为60.71%、28.56%。不同浓度的小檗碱对MDM2mRNA表达阳性细胞的生长抑制率明显高于MDM2mRNA表达阴性细胞(P<0.05),而在P53mRNA阳性表达的细胞中未发现类似结果。
结论：小檗碱对白血病细胞的生长抑制与MDM2mRNA的表达有关,而与P53mRNA的表达无关。
目的：由于儿童白血病细胞的抗原表达与正常造血细胞不同,常会丢失正常应有的抗原,或表达正常不应有的抗原,甚至表达其他抗原,目前尚未发现其特异性抗原。为此,本研究对本院2000年1月-2009年4月收治的195例急性白血病(AL)患儿免疫分型的资料进行分析,并与其临床特征进行比较。
方法：取肝素抗凝的骨髓或静脉血2-3 ml,利用流式细胞仪进行免疫分型检测。AL患儿首次诱导缓解采用的治疗方案：急性淋巴细胞白血病(ALL)采用VDLP[长春新碱(V)、柔红霉素(D)、左旋门冬酰氨酶(L)、强的松(P)]方案；而急性髓性细胞白血病(AML)采用DA[柔红霉素(D)、阿糖胞苷(A)]或DAE[依托泊苷(E)]或ARTA(全反式维甲酸)+DA方案。
结果：
1.195例AL中ALL 139例(71.28%),AML42例(21.54%),急性混合细胞型白血病(AMLL)14例(7.18%)。139例ALL中B-ALL103例(74.1%),T-ALL24例(17.27%),T/B双表型12例(8.63%)。42例AML中M 12例(4.76%),M 217例(40.78%),M 312例(28.57%),M 44例(9.52%),M 57例(16.67%)。本研究免疫分型与FAB分型的符合率为92.82%。
2. B-ALL主要表达的抗原有CD19(90.29%)、CD10(83.50%)、CD20(27.18%)。T-ALL主要表达的抗原有CD3(79.17%)、CD7(66.67%)、CD5(33.33%)。B/T-ALL主要表达的T系抗原有CD7(50%)、CD5(41.67%)；B系抗原有CD19(50%)、CD10(33.33%)。139例ALL中32例有髓系抗原表达,主要表达的抗原有CD13、CD33、CD14、MPO等,而CD15未见表达。139例ALL中31例表达CD34;而My+ALL中CD34阳性表达(15.62%)明显低于My-ALL (24.30%)。139例ALL中82例表达HLA-DR。
3.42例AML主要表达的抗原有CD13(64.29%)、CD33(59.52%)、MPO(42.86%)、CD15(33.33%)。其中M1主要表达的抗原有CD13、CD117、CD15; M2主要表达的抗原有CD13、CD33、MPO。M3主要表达的抗原有CD13、CD33、MPO。M4主要表达的抗原有CD13、CD33、CD15。M5主要表达的抗原有CD14。13例AML主要表达的淋系抗原有CD19、CD7、CD3。42例AML中15例表达CD34,最常见于M1、M2；而Ly+AML中CD34阳性表达率与Ly-AML比较无差异(p＞0.05)。42例AML中25例表达HLA-DR,最常见于M1、M2、M4、M5。
4.14例AMLL主要表达的B系抗原有CD19、CD10、CD22;主要表达的T系抗原有CD7、CD3、CD5;主要表达的髓系抗原表达有CD13、CD14、CD33、CD15。14例AMLL中9例接受化疗,首次化疗后6例达到完全缓解(CR),其CR率为66.67%,低于ALL、AML。14例AML中2例表达CD34；7例表达HLA-DR。
5. My+ALL组性别、出血情况与My-ALL组比较均有显著差异(χ2=4.20,20.03P均<0.05),而其余指标均无差异(P＞0.05)；而My+ALL组CR率(56.25%)与My ALL组(57.94%)比较无差异(χ2=0.03 P＞0.05)。Ly+-AML组肝大例数与Ly-AML比较有差异(χ2=6.48 P<0.05),而其余指标均无差异(P＞0.05)而Ly+AML组CR率(38.46%)与Ly-ALL组(31.03%)比较差异无差异(χ2=3.84 P＞0.05)。
结论：
1.免疫分型可正确区分儿童白血病细胞的来源,且能弥补形态学分型的部分不足。
2.由于CD13、CD33、MPO可表达于ALL中,而CD15仅表达于AML,因此CD15髓系抗原的特异性优于CD13、CD33、MPO,可作为鉴别儿童ALL与AML的重要标记。
3. My+ALL主要表达的抗原有CD13、CD33、CD14。Ly+AML主要表达的抗原有CD19、CD3、CD7。ALL伴髓系抗原表达、AML伴淋系抗原表达分别与ALL、AML的预后无关。
4. AMLL是一种具有髓系和淋系共同表达独特的AL,与Ly+AML和My+ALL不同,且预后较ALL、AML差。
目的：综合评价亚甲基四氢叶酸还原酶(MTHFR)基因多态性与儿童急性白血病(AL)的关系。
方法：以AL组和对照组MTHFR基因677、1298位点的基因型例数为统计量,全面检索、筛选相关文献,提取研究数据结果和选择基因位点,首先进行异质性检验；对存在异质性者,按照AL类型和来源人群进行亚组分析；应用RevMan 4.2对各研究结果进行数据合并,计算OR值及其95%CI,并进行统计学处理；同时利用漏斗图进行发表偏倚分析；利用改变样本量对各研究结果进行敏感性分析。
结果：
共检索有效文献17篇,除MTHFR基因677位点TT型的各研究间不存在异质性外(P>0.05),其他基因型的各研究间均存在异质性。MTHFR基因677位点TT在AL的分布频率显著高于对照组外,其OR及95%CI为0.81(0.69-0.97)(P<0.05),而AL组MTHFR基因677位点CT、TT+CT的分布频率与对照组比较,无显著差异(P>0.05)。MTHFR基因1298位点AC、CC、AC+CC在AL的分布频率与对照组比较,无差异,其OR值及95%CI分别为1.11(0.83-1.49)、1.15(0.93-1.42)、1.18(0.95-1.46)(P均>0.05)。
亚组分析：1.白血病类型：对MTHFR基因677位点CT、TT+CT与ALL关系的文献进行分析,结果Z为1.43,1.74,P均>0.05；而对MTHFR基因677位点CT、TT+CT与ANLL关系的文献进行分析,结果Z为0.69,0.37,P均>0.05。对纳入MTHFR基因1298位点多态性与ALL、ANLL关系的文献进行分析,结果提示MTHFR基因1298位点多态性与ALL、ANLL均无关。2.来源人群：亚洲人群：MTHFR基因1298位点AC+CC与AL的结果为Z=2.01，P均<0.05。欧洲人群：对MTHFR基因677位点CT、CT+TT与AL关系的文献进行分析,结果Z=2.63,2.07,P均<0.05。对MTHFR基因1298位点CC与AL关系的文献进行分析,结果Z为=1.93,P=0.05。其他人群：MTHFRC基因677、1298位点多态与AL均无关。发表偏倚分析和敏感性分析结果均提示本文的结果是稳定与可靠的。
结论：MTHFR基因677位点TT有利于儿童AL发生；CT、CT+TT也是导致欧洲儿童发生AL的危险因素。MTHFR基因1298位点CC是欧洲儿童发生AL的保护因素,而AC+CC则是导致亚洲人群儿童发生AL的危险因素。
目的：探讨细胞色素P4501A1 (CYP1A1) MspⅠ基因多态性与儿童急性白血病(AL)的关系。
方法：以AL组和正常对照组的CYP1A1 MspⅠ基因型例数为统计量,全面检索、筛选相关文献,提取研究数据结果和选择基因位点,进行异质性检验,按照AL类型和来源人群进行亚组分析；应用RevMan4.2对各研究结果进行计算合并OR值及其95%CI,并利用漏斗图进行发表偏倚分析。
结果：共检索符合条件的文献6篇,其中AL组837例,对照组1252例。异质性检验结果：除杂合子型不存在异质性外(χ2=11.68 P>0.05),余两型均存在异质性(χ2=16.38,14.77 P均<0.05)。根据异质性检验结果,利用固定或随机效应模型估计,以CYP1A1 MspⅠ野生纯合子为参照组,杂合子、突变纯合子、杂合子+突变纯合子的合并OR分别为1.18(0.9-1.49)、0.96(0.31-3.00)、1.10(0.77-1.57)。对存在异质性的突变纯合子、杂合子+突变纯合子进行亚组分析,结果提示CYP1A1 MspⅠ基因突变纯合子、杂合子+突变纯合子型与急性淋巴细胞白血病关系合并分析的Z=0.10,0.76 P均>0.05; CYP1A1 MspⅠ基因突变纯合子、杂合子+突变纯合子型与急性非淋巴细胞白血病关系合并分析的Z=0.74,0.75 P均>0.05。
结论：CYP1A1 MspⅠ基因多态性与儿童AL的发生无关。
目的：探讨母亲怀孕过程中饮酒与儿童急性白血病(AL)发生的关系,为预防白血病提供依据。
方法：以母亲怀孕过程中儿童AL组和对照组饮酒的例数为统计量,全面检索、筛选相关文献,提取研究数据结果,进行异质性检验,按照AL类型进行亚组分析；应用RevMan 4.2对各研究结果进行数据合并,计算合并OR值及其95%CI,并进行统计学处理；同时利用漏斗图进行发表偏倚分析。
结果：共纳入有效文献10篇,其中AL组4593例,对照组6157例。根据两组异质性检验结果(χ2=16.26 P<0.05),采用随机效应模型计算,结果提示合并OR值及95%CI为1.02(0.92-1.14),Z=0.41,P=0.68>0.05,提示两组差异无统计学意义。亚组分析：对母亲怀孕过程中饮酒与儿童急性淋巴细胞白血病(ALL)关系的6篇文献进行,合并分析的OR值及95%CI为0.92(0.84-1.00),Z=1.92,P=0.05,提示两组差异有统计学意义。而对母亲怀孕过程中饮酒与儿童急性非淋巴细胞白血病(ANLL)关系的4篇文献进行合并分析,合并OR值及95%CI为0.82(0.61-1.11),Z=1.30,P=0.19>0.05,提示两组差异无统计学意义。
结论：母亲怀孕过程中饮酒与儿童ALL的发生有关,但与ANLL发生无关。
Objective:Leukemia cell lines were usually used as research target in most childhood leukemia study, however, cell lines were lack of cell heterogeneity and easy to mutate, which affect of the experimental accuracy. To provide biologically and genetically similar cells as those in vivo, we explored the isolation and culture methods in childhood primary leukemia cells and proposed the optimal cultivation methods. Our study serves as important references in childhood leukemia study in vitro.
Methods:The primary leukemia cells were collected from 25 children with acute leukemia. The primary leukemia cells were isolated by human lymphocyte separation medium. The cell morphology was observed by inverted microscope. The cell proliferation activities were analyzed by CCK-8 method under various cell densities and cell culture medium.
Results:Cell morphology and CCK-8 shows that the primary leukemia cells have higher viability within 72 h. Cells at high density [(4-10)×106/ml]have higher cell proliferation than those at low density[(1-2)×106/ml]. The fetal bovine serum was better for primary cell proliferation than patients' own serum (P<0.05)
Conclusions:The primary leukemic cell can be successfully isolated by human lymphocyte separation medium.6×106/ml planting density and 10% fetal bovine serum medium were the most optimal culture condition for primary leukemia cells.
Objective:To investigate berberine-induced cell proliferation and apoptosis in childhood primary leukemia.
Methods:The primary leukemic cells were isolated from bone marrow or peripheral blood by human lymphocyte separation medium in 27 children with newly diagnosed acute leukemia. These primary leukemic cells were divided into the following four groups:(1) the control group,(2) 25uM berberine group, (3)50uM berberine group,(4) 100 uM berberine group. Primary leukemic cell proliferation inhibition rate of berberine was obtained by cell counting kit-8 assay (CCK-8) at 24 h,48 h, and 72 h. The berberine-induced apoptosis of primary leukemia cells was analyzed by flow cytometry and optical microscopy at 24h.
Results:After 24,48,72 h treatment of berberine, proliferation of primary leukemia cell were remarkably inhibited in a time-and dose-dependent manner, which was of significant differences (F=125.86,12.67 P<0.01). Cell morphology changes and typical apoptotsis were observed under optical microscope at 24h of berberine treatment. The berberine induced apoptotic rates at 25 uM,50 uM,100 uM were 28.51%,31.98%,48.60% at 24 h, which was detected by flow cytometry.
Conclusion:Berberine induces apoptosis and inhibits the proliferation of primary leukemia cells in a time-and dose-dependent manner.
Objective:To explore the relationship of MDM2, P53 gene expression and cell growth inhibition of berberine in childhood leukemic cell.
Methods:Forty patients with newly diagnosed childhood leukemia were collected from Department of Pediatrics, Tongji Hospital as research objective, and leukemic cells were isolated by human lymphoid separation liquid, and leukemia cell growth inhibition rate of berberine was detected by CCK-8 methods. MDM2, P53 mRNA expression were detected by RT-PCR; MDM2, P53 protein expression were detected by immunohistochemistry in leukemia cells. The correlations between cell growth inhibition rate and the expression of MDM2mRNA, P53mRNA were investigated.
Results:The higher expression of MDM2, P53 gene were observed in childhood leukemia. After 24 h of treatment, berberine induced cell growth inhibition in various concentration in MDM2 positive cells were significantly higher than that in MDM2-negative cells, while similar results was not found in P53 positive cells.
Conclusion:Berberine may inhibit the growth of leukemia cells, which is correlated with the expression of MDM2, but not with the expression of P53.
Objective:As the antigen expression in leukemic cells are not necessarily the same as normal hematopoietic cells. leukemic cells were often lost those normal antigens present those abnormal antigen. No specific antigen patterns were found in childhood leukemia cells. To solve the problem, we analyzed immunophenotype reaults which were detected by flow cytometry in childhood acute leukemia (AL) and compared with their clinical data.
Methods:2-3 ml bone marrow or blood with heparin anticoagulation from children were used to test immunophenotype classification by flow cytometry. The first remissions were inducted by VDLP in ALL children, while in children with AML were DA or DAE or ARTA+DA schema.
Results:
1. According to characteristics of the immunophenotype in 195 AL children, the number of ALL was 139 cases (71.28%), AML were 42 cases (21.54%); AMLL 14 cases (7.18%). In 139 ALL children, B-ALL 103 cases (74.1%), T-ALL 24 cases (17.27%), T/B biphenotypic 12 cases (8.63%).In 42 children of AML, the incidence rate of M2 was the highest (40.78%), followed by M3(28.57%), M5 (16.67%), M4 (9.52%), M1 (4.76%). In this study, the consistent diagnosis rate with FAB classification was 92.82%.
2. In 103 children of B-ALL, expression of the major antigen were CD19 (90.29%), CD10 (83.50%), CD20 (27.18%); In 24 children with T-ALL, expression of the major antigens were CD3 (79.17%), CD7 (66.67%), CD5 (33.33%). In 12 cases of B/T-ALL, the expression of T-lymphoid antigens were CD7 (50%), CD5 (41.67%), while the B lymphoid antigens were CD19 (50%), CD10 (33.33%). In 139 children of ALL, myeloid antigen expression (My+ALL) was 32 cases(23.02%), and the main expression antigen were CD 13, CD33, CD 14, MPO and CD 15 was not expressed; In 139 children of ALL, expression of CD34 in 31 cases with ALL, followed by T/B-ALL, B-ALL, T-ALL. CD34-positive expression (15.62%) in My+ALL was significantly lower than that of My-ALL (24.30%). In 82 cases of HLA-DR expression, the sequence was B-ALL, T/ B-ALL, T-ALL.
3. In 42 children of AML, the major antigen were CD13 (64.29%), CD33 (59.52%), MPO (42.86%), CD15 (33.33%). For expression of CD13, CD33, MPO in all of ALL, whereas no expression of CD 15, the myeloid lineage specificity of CD 15 was superior to that of CD13, CD33, MPO. In M1, CD13, CD117, CD15 were mainly expressed; M2 was CD13, CD33, MPO. M3 was CD13, CD33, MPO. M4 was CD13, CD33, CD15. M5 was CD 14. In 13 children of AML were associated with lymphoid antigen expression of CD 19, CD7, CD3. In 42 cases of AML, expression of CD34 was 15 cases, which were the most common in M1, M2. Ly+ AML in the CD34-positive expression of Ly-AML was not different from that of Ly+ AML.And expression of HLA-DR was 25 cases, which were the most common in M1, M2, M4, M5.
4. In 14 cases of AMLL, the main expression of B lineage antigens were CD 19, CD 10, CD22;the main expression of T antigens were CD7, CD3, CD5; myeloid antigen expression were CD13, CD14, CD33, CD15. Nine cases received chemotherapy in 14 cases of AMLL,6 patients achieved complete remission (CR) (66.67%) after first chemotherapy, which was lower than that of ALL and AML. In 14 cases of AML,2 cases expressed CD34; 7 cases expressed HLA-DR.
5. The number of sex, bleeding in My+ALL group and My-ALL group were significantly different (x2=4.20,20.03 P<0.05), while the other indexes wasnot different significantly (P>0.05). CR rate (56.25%) of My+ALL group and My-ALL group (57.94%) have more differences (x2= 6.18 P<0.05). The number of cases of liver large in Ly+AML group compared with in the Ly-AML are different (x2= 6.48 P<0.05), while the other indexes did not differ significantly (P>0.05). CR rate (31.03%) in Ly+AML group and Ly-ALL group was not also different (x2= 0.15 P> 0.05).
Conclusions:
1. Immunetyping helps to differentiate the sources of leukemic cells, and helps to get the correct typing in most cases of childhood leukemia.
2. To identify ALL and AML, the myeloid lineage specificity of CD 15 is superior to that of CD13, CD33 and MPO.
3. HLA-DR negative could be of certain value in the diagnosis of AML M3.
4. In My+ALL, the major expression of myeloid antigens was CD13 and CD33. And in Ly+AML, the major expression of lymphoid expression are CD 19, CD3. And the myeloid expression and the lymphoid expression are not related with their prognosis.
5. AMLL is a unique acute leukemia expresses both myeloid and lymphoid antigen, which has worse prognosis than either AML or ALL.
Objective:To evaluate of the correlations of methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and childhood acute leukemia (AL).
Methods:MTHFR gene C677T and A1298C genotype frequencies in children with AL and control group were used as statistical quantity. Relevant literatures were extensively searched and screened according to the type of leukemia and population subgroup. These results of research data were extracted and the gene loci were tested for heterogeneity. Various research datas consolidation, combined OR values and their 95% CI were statistically tested by RevMan 4.2; Funnel plots was used for the bias analysis of published literature; sample size alteration were used to analyze the results sensitivity in order to evaluate the stability of Meta analysis.
Results:Seventeen literatures were searched for Meta analysis. Except for MTHFR gene 677 loci genotype TT had no heterogeneity (P>0.05), the other MTHFR gene 677 loci genotypes all had heterogeneity. the frequency distribution of MTHFR gene 677 loci genotype TT in AL group was significantly higher than that in control group, and it's combined OR values and 95% CI were 0.81(0.69-0.97)(P<0.05). MTHFR gene 677 loci genotype CT, TT+CT of the frequency in AL group compared with that in control group had no significant difference (P>0.05). Compared to control group, there were no significant difference of frequency distribution of MTHFR gene 1298 loci AC, CC, AC+ CC in pediatric AL group. Combined OR values and 95%CI were 1.11 (0.83-1.49),1.15 (0.93-1.42),1.18 (0.95-1.46) (P>0.05).
Subgroup analysis:1.the results suggest that MTHFR 677 loci CT, CT+TT and 1298 loci AC, CC, AC+CC were not correlated with ALL; In ANLL group, analysis results indicated that MTHFR gene polymorphism in ANLL group has nothing to do with control group.2. The analysis results suggested that MTHFR1298 loci CC, AC+CC was related with childhood AL in Asian populations (Z=2.05,2.01,P<0.05) while in Europe population, MTHFR 677 loci CT, CT+TT was related with childhood AL (Z=2.91,2.08,P <0.05).In other population, MTHFR677,1298 was not related with childhood AL. The bias and sensitivity analysis confirmed that the Meta analysis of the publicated literatures in this article werestable and reliable.
Conclusions:MTHFR gene 677 loci TT is closely related with pediatric AL; And MTHFR gene 677 CT, CT+TT are also contributed to the occurrence of AL in European children. MTHFR gene 1298 loci CC is the protective factors of AL in European children, and MTHFR gene 1298 loci AC+CC can led to the occurrence of AL in the Asian children.
Objective:To investigate the relationship of cytochrome P4501A1 (CYP1 A1) MspⅠgene polymorphism and childhood acute leukemia (AL).
Methods:The CYP1 A1 MspⅠgene frequencies were used as statistical quantity in AL and control group. Relevant literatures were extensively searched and screened according to the type of leukemia and the subgroup of population. These results of research data were extracted and the gene loci were tested for heterogeneity. Various research datas consolidation, combined OR values and their 95% CI were statistically tested by RevMan 4.2; Funnel plots was used for the bias analysis of published literature.
Results:Six related literatures were found to meet the requirements of screen,including 837 cases in AL group and 1252 cases in control group. According to heterogeneity test result, there was no significant difference (x2=11.68, P>0.05)in homozygous types, but in two others types, there were significant difference (x2= 16.38,14.77, P all<0.05). For the wild CYP1A1 MspⅠhomozygous for the reference group, the combined OR of heterozygous mutation, homozygous, heterozygous + homozygous mutation in AL and control groups were 1.18(0.94-1.49),0.96(0.31-3.00),1.10(0.77-1.57). Subgroup analysis: combined analysis(Z value) of CYP1A1 MspⅠhomozygous, heterozygous + homozygous in acute lymphoblastic leukemia (ALL) and control group were 0.10,0.76 respectively, P all > 0.05; Z value of CYP1A1 MspⅠhomozygous, heterozygous + homozygous in non-acute lymphoblastic leukemia (ANLL) and control group were 0.74,0.75, P all> 0.05.
Conclusion:There is no correlation between CYP1 A1 MspⅠgene polymorphism and the susceptibility of pediatric AL.
Objective:To explore the relationship between maternal alcohol consumption during pregnancy and childhood acute leukemia (AL), which provides a basis for the prevention of childhood AL.
Methods:These relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened in AL group and control group, and according to the type of leukemic subgroup, Meta analysis was used. These results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. The combined OR values and their 95%CI were statistically tested by Rev Man 4.2; and the funnel plots was used for the bias analysis of all the published literatures.
Results:Ten pieces of related literatures meeted the requirements of data screen. The number of AL cases and control group were 4593 and 6157 respectively. According to heterogeneity test result, there was difference (x2= 16.26, P<0.05), and combined OR values and 95% CI in AL and control group by random effects model were 1.00 (0.90-1.11), and the total effect Z value was 0.02, P>0.05. Subgroup analysis:combined OR values and 95% CI in childhood acute lymphoblastic leukemia (ALL) and control group were 0.92 (0.84-1.00), and the total effect (Z value) of the results was 1.92, P= 0.05. Combined OR values and 95% CI in childhood acute nonlymphoblastic leukemia (ANLL) and control group were 0.82(0.61-1.11), and the total effect (Z value) of the results was 1.30, P> 0.05.
Conclusion:Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in ANLL.
方法：选取2008年8月-2009年9月本院儿科收治的25例初诊AL患儿作为研究对象。于治疗前抽取肝素抗凝的骨髓液或外周血2-3 ml于无菌离心管中,利用人淋巴细胞分离液即可分离出白血病细胞。在倒置光学显微镜下观察不同时间点的原代白血病细胞的形态变化,以及利用CCK-8法检测不同细胞密度、不同成分的培养液对原代白血病细胞增殖活性的影响。
结果：细胞形态学观察及细胞增殖活力测定提示：原代白血病细胞在72 h以内存活率较高；高密度细胞[(4-10)×106/ml]培养低于密度细胞[(1-2)×106/ml]；胎牛血清较患儿自身的血清更有利于原代白血病细胞生长。
结论：利用人淋巴细胞分离液可以成功地分离出原代白血病细胞,而对于原代白血病细胞的体外培养,选择(4-6)×106/ml细胞密度接种于含10%胎牛血清的培养基中生长效果最理想。
目的：探讨小檗碱诱导儿童原代白血病细胞增殖、凋亡的作用。
方法：取初诊的22例白血病患儿的骨髓或外周血2-3 ml,用人淋巴细胞分离液分离出原代白血病细胞。将其分为：(1)对照组；(2)25 uM小檗碱；(3)50uM小檗碱；(4)100uM小檗碱。于24、48、72h时,利用CCK-8法检测小檗碱对每组原代白血病细胞的生长抑制率；同时24 h采用流式细胞术PI染色法及倒置显微镜观察不同浓度小檗碱诱导原代白血病细胞凋亡的影响。
结果：不同浓度(25、50、100 uM)的小檗碱作用于原代白血病细胞24、48、72h后,CCK-8法检测的每组细胞生长抑制率有明显差异(F=125.86,12.67 P均<0.01)。利用光学显微镜观察：细胞作用24 h已发生典型的凋亡变化。流式细胞术PI染色结果提示25、50、100 uM小檗碱作用原代细胞24 h后,其凋亡率分别为28.51%、31.98%、48.60%。
结论：小檗碱具有诱导儿童原代白血病细胞凋亡并抑制细胞增殖的作用,且呈剂量、时间依赖性。
目的：探讨儿童急性白血病细胞MDM2、P53基因表达及其与小檗碱对白血病原代细胞生长抑制的关系。
方法：选取本院儿科收治的40例初诊AL患儿作为研究对象,利用人淋巴细胞分离液分离出原代白血病细胞,并用CCK-8法检测不同浓度小檗碱作用原代白血病细胞24 h的细胞生长抑制率。RT-PCR法和免疫组织化学法检测MDM2、P53在白血病细胞中的表达,并比较MDM2、P53mRNA的表达与小檗碱对原代白血病细胞生长抑制的关系。
结果：儿童白血病中存在MDM2、P53的表达,其中MDM2、P53蛋白阳性率分别为66.67%、22.78%,而MDM2、P53mRNA的表达率分别为60.71%、28.56%。不同浓度的小檗碱对MDM2mRNA表达阳性细胞的生长抑制率明显高于MDM2mRNA表达阴性细胞(P<0.05),而在P53mRNA阳性表达的细胞中未发现类似结果。
结论：小檗碱对白血病细胞的生长抑制与MDM2mRNA的表达有关,而与P53mRNA的表达无关。
目的：由于儿童白血病细胞的抗原表达与正常造血细胞不同,常会丢失正常应有的抗原,或表达正常不应有的抗原,甚至表达其他抗原,目前尚未发现其特异性抗原。为此,本研究对本院2000年1月-2009年4月收治的195例急性白血病(AL)患儿免疫分型的资料进行分析,并与其临床特征进行比较。
方法：取肝素抗凝的骨髓或静脉血2-3 ml,利用流式细胞仪进行免疫分型检测。AL患儿首次诱导缓解采用的治疗方案：急性淋巴细胞白血病(ALL)采用VDLP[长春新碱(V)、柔红霉素(D)、左旋门冬酰氨酶(L)、强的松(P)]方案；而急性髓性细胞白血病(AML)采用DA[柔红霉素(D)、阿糖胞苷(A)]或DAE[依托泊苷(E)]或ARTA(全反式维甲酸)+DA方案。
结果：
1.195例AL中ALL 139例(71.28%),AML42例(21.54%),急性混合细胞型白血病(AMLL)14例(7.18%)。139例ALL中B-ALL103例(74.1%),T-ALL24例(17.27%),T/B双表型12例(8.63%)。42例AML中M 12例(4.76%),M 217例(40.78%),M 312例(28.57%),M 44例(9.52%),M 57例(16.67%)。本研究免疫分型与FAB分型的符合率为92.82%。
2. B-ALL主要表达的抗原有CD19(90.29%)、CD10(83.50%)、CD20(27.18%)。T-ALL主要表达的抗原有CD3(79.17%)、CD7(66.67%)、CD5(33.33%)。B/T-ALL主要表达的T系抗原有CD7(50%)、CD5(41.67%)；B系抗原有CD19(50%)、CD10(33.33%)。139例ALL中32例有髓系抗原表达,主要表达的抗原有CD13、CD33、CD14、MPO等,而CD15未见表达。139例ALL中31例表达CD34;而My+ALL中CD34阳性表达(15.62%)明显低于My-ALL (24.30%)。139例ALL中82例表达HLA-DR。
3.42例AML主要表达的抗原有CD13(64.29%)、CD33(59.52%)、MPO(42.86%)、CD15(33.33%)。其中M1主要表达的抗原有CD13、CD117、CD15; M2主要表达的抗原有CD13、CD33、MPO。M3主要表达的抗原有CD13、CD33、MPO。M4主要表达的抗原有CD13、CD33、CD15。M5主要表达的抗原有CD14。13例AML主要表达的淋系抗原有CD19、CD7、CD3。42例AML中15例表达CD34,最常见于M1、M2；而Ly+AML中CD34阳性表达率与Ly-AML比较无差异(p＞0.05)。42例AML中25例表达HLA-DR,最常见于M1、M2、M4、M5。
4.14例AMLL主要表达的B系抗原有CD19、CD10、CD22;主要表达的T系抗原有CD7、CD3、CD5;主要表达的髓系抗原表达有CD13、CD14、CD33、CD15。14例AMLL中9例接受化疗,首次化疗后6例达到完全缓解(CR),其CR率为66.67%,低于ALL、AML。14例AML中2例表达CD34；7例表达HLA-DR。
5. My+ALL组性别、出血情况与My-ALL组比较均有显著差异(χ2=4.20,20.03P均<0.05),而其余指标均无差异(P＞0.05)；而My+ALL组CR率(56.25%)与My ALL组(57.94%)比较无差异(χ2=0.03 P＞0.05)。Ly+-AML组肝大例数与Ly-AML比较有差异(χ2=6.48 P<0.05),而其余指标均无差异(P＞0.05)而Ly+AML组CR率(38.46%)与Ly-ALL组(31.03%)比较差异无差异(χ2=3.84 P＞0.05)。
结论：
1.免疫分型可正确区分儿童白血病细胞的来源,且能弥补形态学分型的部分不足。
2.由于CD13、CD33、MPO可表达于ALL中,而CD15仅表达于AML,因此CD15髓系抗原的特异性优于CD13、CD33、MPO,可作为鉴别儿童ALL与AML的重要标记。
3. My+ALL主要表达的抗原有CD13、CD33、CD14。Ly+AML主要表达的抗原有CD19、CD3、CD7。ALL伴髓系抗原表达、AML伴淋系抗原表达分别与ALL、AML的预后无关。
4. AMLL是一种具有髓系和淋系共同表达独特的AL,与Ly+AML和My+ALL不同,且预后较ALL、AML差。
目的：综合评价亚甲基四氢叶酸还原酶(MTHFR)基因多态性与儿童急性白血病(AL)的关系。
方法：以AL组和对照组MTHFR基因677、1298位点的基因型例数为统计量,全面检索、筛选相关文献,提取研究数据结果和选择基因位点,首先进行异质性检验；对存在异质性者,按照AL类型和来源人群进行亚组分析；应用RevMan 4.2对各研究结果进行数据合并,计算OR值及其95%CI,并进行统计学处理；同时利用漏斗图进行发表偏倚分析；利用改变样本量对各研究结果进行敏感性分析。
结果：
共检索有效文献17篇,除MTHFR基因677位点TT型的各研究间不存在异质性外(P>0.05),其他基因型的各研究间均存在异质性。MTHFR基因677位点TT在AL的分布频率显著高于对照组外,其OR及95%CI为0.81(0.69-0.97)(P<0.05),而AL组MTHFR基因677位点CT、TT+CT的分布频率与对照组比较,无显著差异(P>0.05)。MTHFR基因1298位点AC、CC、AC+CC在AL的分布频率与对照组比较,无差异,其OR值及95%CI分别为1.11(0.83-1.49)、1.15(0.93-1.42)、1.18(0.95-1.46)(P均>0.05)。
亚组分析：1.白血病类型：对MTHFR基因677位点CT、TT+CT与ALL关系的文献进行分析,结果Z为1.43,1.74,P均>0.05；而对MTHFR基因677位点CT、TT+CT与ANLL关系的文献进行分析,结果Z为0.69,0.37,P均>0.05。对纳入MTHFR基因1298位点多态性与ALL、ANLL关系的文献进行分析,结果提示MTHFR基因1298位点多态性与ALL、ANLL均无关。2.来源人群：亚洲人群：MTHFR基因1298位点AC+CC与AL的结果为Z=2.01，P均<0.05。欧洲人群：对MTHFR基因677位点CT、CT+TT与AL关系的文献进行分析,结果Z=2.63,2.07,P均<0.05。对MTHFR基因1298位点CC与AL关系的文献进行分析,结果Z为=1.93,P=0.05。其他人群：MTHFRC基因677、1298位点多态与AL均无关。发表偏倚分析和敏感性分析结果均提示本文的结果是稳定与可靠的。
结论：MTHFR基因677位点TT有利于儿童AL发生；CT、CT+TT也是导致欧洲儿童发生AL的危险因素。MTHFR基因1298位点CC是欧洲儿童发生AL的保护因素,而AC+CC则是导致亚洲人群儿童发生AL的危险因素。
目的：探讨细胞色素P4501A1 (CYP1A1) MspⅠ基因多态性与儿童急性白血病(AL)的关系。
方法：以AL组和正常对照组的CYP1A1 MspⅠ基因型例数为统计量,全面检索、筛选相关文献,提取研究数据结果和选择基因位点,进行异质性检验,按照AL类型和来源人群进行亚组分析；应用RevMan4.2对各研究结果进行计算合并OR值及其95%CI,并利用漏斗图进行发表偏倚分析。
结果：共检索符合条件的文献6篇,其中AL组837例,对照组1252例。异质性检验结果：除杂合子型不存在异质性外(χ2=11.68 P>0.05),余两型均存在异质性(χ2=16.38,14.77 P均<0.05)。根据异质性检验结果,利用固定或随机效应模型估计,以CYP1A1 MspⅠ野生纯合子为参照组,杂合子、突变纯合子、杂合子+突变纯合子的合并OR分别为1.18(0.9-1.49)、0.96(0.31-3.00)、1.10(0.77-1.57)。对存在异质性的突变纯合子、杂合子+突变纯合子进行亚组分析,结果提示CYP1A1 MspⅠ基因突变纯合子、杂合子+突变纯合子型与急性淋巴细胞白血病关系合并分析的Z=0.10,0.76 P均>0.05; CYP1A1 MspⅠ基因突变纯合子、杂合子+突变纯合子型与急性非淋巴细胞白血病关系合并分析的Z=0.74,0.75 P均>0.05。
结论：CYP1A1 MspⅠ基因多态性与儿童AL的发生无关。
目的：探讨母亲怀孕过程中饮酒与儿童急性白血病(AL)发生的关系,为预防白血病提供依据。
方法：以母亲怀孕过程中儿童AL组和对照组饮酒的例数为统计量,全面检索、筛选相关文献,提取研究数据结果,进行异质性检验,按照AL类型进行亚组分析；应用RevMan 4.2对各研究结果进行数据合并,计算合并OR值及其95%CI,并进行统计学处理；同时利用漏斗图进行发表偏倚分析。
结果：共纳入有效文献10篇,其中AL组4593例,对照组6157例。根据两组异质性检验结果(χ2=16.26 P<0.05),采用随机效应模型计算,结果提示合并OR值及95%CI为1.02(0.92-1.14),Z=0.41,P=0.68>0.05,提示两组差异无统计学意义。亚组分析：对母亲怀孕过程中饮酒与儿童急性淋巴细胞白血病(ALL)关系的6篇文献进行,合并分析的OR值及95%CI为0.92(0.84-1.00),Z=1.92,P=0.05,提示两组差异有统计学意义。而对母亲怀孕过程中饮酒与儿童急性非淋巴细胞白血病(ANLL)关系的4篇文献进行合并分析,合并OR值及95%CI为0.82(0.61-1.11),Z=1.30,P=0.19>0.05,提示两组差异无统计学意义。
结论：母亲怀孕过程中饮酒与儿童ALL的发生有关,但与ANLL发生无关。
Objective:Leukemia cell lines were usually used as research target in most childhood leukemia study, however, cell lines were lack of cell heterogeneity and easy to mutate, which affect of the experimental accuracy. To provide biologically and genetically similar cells as those in vivo, we explored the isolation and culture methods in childhood primary leukemia cells and proposed the optimal cultivation methods. Our study serves as important references in childhood leukemia study in vitro.
Methods:The primary leukemia cells were collected from 25 children with acute leukemia. The primary leukemia cells were isolated by human lymphocyte separation medium. The cell morphology was observed by inverted microscope. The cell proliferation activities were analyzed by CCK-8 method under various cell densities and cell culture medium.
Results:Cell morphology and CCK-8 shows that the primary leukemia cells have higher viability within 72 h. Cells at high density [(4-10)×106/ml]have higher cell proliferation than those at low density[(1-2)×106/ml]. The fetal bovine serum was better for primary cell proliferation than patients' own serum (P<0.05)
Conclusions:The primary leukemic cell can be successfully isolated by human lymphocyte separation medium.6×106/ml planting density and 10% fetal bovine serum medium were the most optimal culture condition for primary leukemia cells.
Objective:To investigate berberine-induced cell proliferation and apoptosis in childhood primary leukemia.
Methods:The primary leukemic cells were isolated from bone marrow or peripheral blood by human lymphocyte separation medium in 27 children with newly diagnosed acute leukemia. These primary leukemic cells were divided into the following four groups:(1) the control group,(2) 25uM berberine group, (3)50uM berberine group,(4) 100 uM berberine group. Primary leukemic cell proliferation inhibition rate of berberine was obtained by cell counting kit-8 assay (CCK-8) at 24 h,48 h, and 72 h. The berberine-induced apoptosis of primary leukemia cells was analyzed by flow cytometry and optical microscopy at 24h.
Results:After 24,48,72 h treatment of berberine, proliferation of primary leukemia cell were remarkably inhibited in a time-and dose-dependent manner, which was of significant differences (F=125.86,12.67 P<0.01). Cell morphology changes and typical apoptotsis were observed under optical microscope at 24h of berberine treatment. The berberine induced apoptotic rates at 25 uM,50 uM,100 uM were 28.51%,31.98%,48.60% at 24 h, which was detected by flow cytometry.
Conclusion:Berberine induces apoptosis and inhibits the proliferation of primary leukemia cells in a time-and dose-dependent manner.
Objective:To explore the relationship of MDM2, P53 gene expression and cell growth inhibition of berberine in childhood leukemic cell.
Methods:Forty patients with newly diagnosed childhood leukemia were collected from Department of Pediatrics, Tongji Hospital as research objective, and leukemic cells were isolated by human lymphoid separation liquid, and leukemia cell growth inhibition rate of berberine was detected by CCK-8 methods. MDM2, P53 mRNA expression were detected by RT-PCR; MDM2, P53 protein expression were detected by immunohistochemistry in leukemia cells. The correlations between cell growth inhibition rate and the expression of MDM2mRNA, P53mRNA were investigated.
Results:The higher expression of MDM2, P53 gene were observed in childhood leukemia. After 24 h of treatment, berberine induced cell growth inhibition in various concentration in MDM2 positive cells were significantly higher than that in MDM2-negative cells, while similar results was not found in P53 positive cells.
Conclusion:Berberine may inhibit the growth of leukemia cells, which is correlated with the expression of MDM2, but not with the expression of P53.
Objective:As the antigen expression in leukemic cells are not necessarily the same as normal hematopoietic cells. leukemic cells were often lost those normal antigens present those abnormal antigen. No specific antigen patterns were found in childhood leukemia cells. To solve the problem, we analyzed immunophenotype reaults which were detected by flow cytometry in childhood acute leukemia (AL) and compared with their clinical data.
Methods:2-3 ml bone marrow or blood with heparin anticoagulation from children were used to test immunophenotype classification by flow cytometry. The first remissions were inducted by VDLP in ALL children, while in children with AML were DA or DAE or ARTA+DA schema.
Results:
1. According to characteristics of the immunophenotype in 195 AL children, the number of ALL was 139 cases (71.28%), AML were 42 cases (21.54%); AMLL 14 cases (7.18%). In 139 ALL children, B-ALL 103 cases (74.1%), T-ALL 24 cases (17.27%), T/B biphenotypic 12 cases (8.63%).In 42 children of AML, the incidence rate of M2 was the highest (40.78%), followed by M3(28.57%), M5 (16.67%), M4 (9.52%), M1 (4.76%). In this study, the consistent diagnosis rate with FAB classification was 92.82%.
2. In 103 children of B-ALL, expression of the major antigen were CD19 (90.29%), CD10 (83.50%), CD20 (27.18%); In 24 children with T-ALL, expression of the major antigens were CD3 (79.17%), CD7 (66.67%), CD5 (33.33%). In 12 cases of B/T-ALL, the expression of T-lymphoid antigens were CD7 (50%), CD5 (41.67%), while the B lymphoid antigens were CD19 (50%), CD10 (33.33%). In 139 children of ALL, myeloid antigen expression (My+ALL) was 32 cases(23.02%), and the main expression antigen were CD 13, CD33, CD 14, MPO and CD 15 was not expressed; In 139 children of ALL, expression of CD34 in 31 cases with ALL, followed by T/B-ALL, B-ALL, T-ALL. CD34-positive expression (15.62%) in My+ALL was significantly lower than that of My-ALL (24.30%). In 82 cases of HLA-DR expression, the sequence was B-ALL, T/ B-ALL, T-ALL.
3. In 42 children of AML, the major antigen were CD13 (64.29%), CD33 (59.52%), MPO (42.86%), CD15 (33.33%). For expression of CD13, CD33, MPO in all of ALL, whereas no expression of CD 15, the myeloid lineage specificity of CD 15 was superior to that of CD13, CD33, MPO. In M1, CD13, CD117, CD15 were mainly expressed; M2 was CD13, CD33, MPO. M3 was CD13, CD33, MPO. M4 was CD13, CD33, CD15. M5 was CD 14. In 13 children of AML were associated with lymphoid antigen expression of CD 19, CD7, CD3. In 42 cases of AML, expression of CD34 was 15 cases, which were the most common in M1, M2. Ly+ AML in the CD34-positive expression of Ly-AML was not different from that of Ly+ AML.And expression of HLA-DR was 25 cases, which were the most common in M1, M2, M4, M5.
4. In 14 cases of AMLL, the main expression of B lineage antigens were CD 19, CD 10, CD22;the main expression of T antigens were CD7, CD3, CD5; myeloid antigen expression were CD13, CD14, CD33, CD15. Nine cases received chemotherapy in 14 cases of AMLL,6 patients achieved complete remission (CR) (66.67%) after first chemotherapy, which was lower than that of ALL and AML. In 14 cases of AML,2 cases expressed CD34; 7 cases expressed HLA-DR.
5. The number of sex, bleeding in My+ALL group and My-ALL group were significantly different (x2=4.20,20.03 P<0.05), while the other indexes wasnot different significantly (P>0.05). CR rate (56.25%) of My+ALL group and My-ALL group (57.94%) have more differences (x2= 6.18 P<0.05). The number of cases of liver large in Ly+AML group compared with in the Ly-AML are different (x2= 6.48 P<0.05), while the other indexes did not differ significantly (P>0.05). CR rate (31.03%) in Ly+AML group and Ly-ALL group was not also different (x2= 0.15 P> 0.05).
Conclusions:
1. Immunetyping helps to differentiate the sources of leukemic cells, and helps to get the correct typing in most cases of childhood leukemia.
2. To identify ALL and AML, the myeloid lineage specificity of CD 15 is superior to that of CD13, CD33 and MPO.
3. HLA-DR negative could be of certain value in the diagnosis of AML M3.
4. In My+ALL, the major expression of myeloid antigens was CD13 and CD33. And in Ly+AML, the major expression of lymphoid expression are CD 19, CD3. And the myeloid expression and the lymphoid expression are not related with their prognosis.
5. AMLL is a unique acute leukemia expresses both myeloid and lymphoid antigen, which has worse prognosis than either AML or ALL.
Objective:To evaluate of the correlations of methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and childhood acute leukemia (AL).
Methods:MTHFR gene C677T and A1298C genotype frequencies in children with AL and control group were used as statistical quantity. Relevant literatures were extensively searched and screened according to the type of leukemia and population subgroup. These results of research data were extracted and the gene loci were tested for heterogeneity. Various research datas consolidation, combined OR values and their 95% CI were statistically tested by RevMan 4.2; Funnel plots was used for the bias analysis of published literature; sample size alteration were used to analyze the results sensitivity in order to evaluate the stability of Meta analysis.
Results:Seventeen literatures were searched for Meta analysis. Except for MTHFR gene 677 loci genotype TT had no heterogeneity (P>0.05), the other MTHFR gene 677 loci genotypes all had heterogeneity. the frequency distribution of MTHFR gene 677 loci genotype TT in AL group was significantly higher than that in control group, and it's combined OR values and 95% CI were 0.81(0.69-0.97)(P<0.05). MTHFR gene 677 loci genotype CT, TT+CT of the frequency in AL group compared with that in control group had no significant difference (P>0.05). Compared to control group, there were no significant difference of frequency distribution of MTHFR gene 1298 loci AC, CC, AC+ CC in pediatric AL group. Combined OR values and 95%CI were 1.11 (0.83-1.49),1.15 (0.93-1.42),1.18 (0.95-1.46) (P>0.05).
Subgroup analysis:1.the results suggest that MTHFR 677 loci CT, CT+TT and 1298 loci AC, CC, AC+CC were not correlated with ALL; In ANLL group, analysis results indicated that MTHFR gene polymorphism in ANLL group has nothing to do with control group.2. The analysis results suggested that MTHFR1298 loci CC, AC+CC was related with childhood AL in Asian populations (Z=2.05,2.01,P<0.05) while in Europe population, MTHFR 677 loci CT, CT+TT was related with childhood AL (Z=2.91,2.08,P <0.05).In other population, MTHFR677,1298 was not related with childhood AL. The bias and sensitivity analysis confirmed that the Meta analysis of the publicated literatures in this article werestable and reliable.
Conclusions:MTHFR gene 677 loci TT is closely related with pediatric AL; And MTHFR gene 677 CT, CT+TT are also contributed to the occurrence of AL in European children. MTHFR gene 1298 loci CC is the protective factors of AL in European children, and MTHFR gene 1298 loci AC+CC can led to the occurrence of AL in the Asian children.
Objective:To investigate the relationship of cytochrome P4501A1 (CYP1 A1) MspⅠgene polymorphism and childhood acute leukemia (AL).
Methods:The CYP1 A1 MspⅠgene frequencies were used as statistical quantity in AL and control group. Relevant literatures were extensively searched and screened according to the type of leukemia and the subgroup of population. These results of research data were extracted and the gene loci were tested for heterogeneity. Various research datas consolidation, combined OR values and their 95% CI were statistically tested by RevMan 4.2; Funnel plots was used for the bias analysis of published literature.
Results:Six related literatures were found to meet the requirements of screen,including 837 cases in AL group and 1252 cases in control group. According to heterogeneity test result, there was no significant difference (x2=11.68, P>0.05)in homozygous types, but in two others types, there were significant difference (x2= 16.38,14.77, P all<0.05). For the wild CYP1A1 MspⅠhomozygous for the reference group, the combined OR of heterozygous mutation, homozygous, heterozygous + homozygous mutation in AL and control groups were 1.18(0.94-1.49),0.96(0.31-3.00),1.10(0.77-1.57). Subgroup analysis: combined analysis(Z value) of CYP1A1 MspⅠhomozygous, heterozygous + homozygous in acute lymphoblastic leukemia (ALL) and control group were 0.10,0.76 respectively, P all > 0.05; Z value of CYP1A1 MspⅠhomozygous, heterozygous + homozygous in non-acute lymphoblastic leukemia (ANLL) and control group were 0.74,0.75, P all> 0.05.
Conclusion:There is no correlation between CYP1 A1 MspⅠgene polymorphism and the susceptibility of pediatric AL.
Objective:To explore the relationship between maternal alcohol consumption during pregnancy and childhood acute leukemia (AL), which provides a basis for the prevention of childhood AL.
Methods:These relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened in AL group and control group, and according to the type of leukemic subgroup, Meta analysis was used. These results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. The combined OR values and their 95%CI were statistically tested by Rev Man 4.2; and the funnel plots was used for the bias analysis of all the published literatures.
Results:Ten pieces of related literatures meeted the requirements of data screen. The number of AL cases and control group were 4593 and 6157 respectively. According to heterogeneity test result, there was difference (x2= 16.26, P<0.05), and combined OR values and 95% CI in AL and control group by random effects model were 1.00 (0.90-1.11), and the total effect Z value was 0.02, P>0.05. Subgroup analysis:combined OR values and 95% CI in childhood acute lymphoblastic leukemia (ALL) and control group were 0.92 (0.84-1.00), and the total effect (Z value) of the results was 1.92, P= 0.05. Combined OR values and 95% CI in childhood acute nonlymphoblastic leukemia (ANLL) and control group were 0.82(0.61-1.11), and the total effect (Z value) of the results was 1.30, P> 0.05.
Conclusion:Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in ANLL.
引文
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