Objective： The authors used a meta-analytic technique to quantify the evidence of an association between ma- ternal alcohol consumption during pregnancy and childhood acute leukemia （AL）, which provided a basis for...Objective： The authors used a meta-analytic technique to quantify the evidence of an association between ma- ternal alcohol consumption during pregnancy and childhood acute leukemia （AL）, which provided a basis for the prevention of childhood AL. Methods： Relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened. Subgroup meta-analysis was conducted according to the type of leukemia. Results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. Combined OR values and 95% CIs were statistically calculated with RevMan 4.2 software; Funnel plots were applied to conduct bias analysis for those included litera- tures. Results： Ten related literatures were included after data screening, 4593 cases in AL group and 6157 cases in control group respectively. According to heterogeneity test result （X2 = 16.26, P 〈 0.05）, the combined OR values and 95% CI were calculated with random effects model, which were 1.02 （0.92-1.14）, Z = 0.41, P = 0.68 〉 0.05, indicating that there was no significant difference between maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia （AL）. Subgroup analysis： for the association between maternal alcohol consumption during pregnancy and childhood acute lympho- blastic leukemia （ALL）, the combined OR value and 95% CI were 0.92 （0.84-1.00）, Z = 1.92, P = 0.05, indicating that there was significant difference between two groups; for the association between maternal alcohol consumption during pregnancy and childhood acute non-lymphoblastic leukemia （ANLL）, the combined OR values and 95% CI were 0.82 （0.61-1.11）, Z = 1.30, P = 0.19 〉 0.05, indicating that there was no significant difference between two groups. Conclusion： Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in childhood ANLL.展开更多
Abstract:Objective To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. Methods We developed ...Abstract:Objective To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. Methods We developed a human model of p210BCR/ABL positive CML by transducing normal human umbilical cord blood CD34+ cells with a retroviral vector containing the b3a2 bcr/abl cDNA. We also examined whether this model recreated the cellular phenotype of CML by assessing cell adhesion, cell migration, cell proliferation and cell survival. Results We found that significantly more myeloid colony forming units grew from p210BCR/ABL expressing cells, adhesion of p210BCR/ABL expressing CD34+ cells to fibronectin was decreased but migration over fibronectin was enhanced compared with mock transduced CD34+ cells. In this model, we showed that the presence of p210BCR/ABL leads to elevated levels of p27kip in p210BCR/ABL expressing CD34+ cells. We also showed that multidrug resistance-1 (MDR-1) Pgp was upregulated in the p210BCR/ABL expressing cells which correlates with the expression of p210BCR/ABL. Conclusion This primary human CML model recreates most of the features of CML and provides a useful tool to study signal transduction and downstream molecular regulation drived by the p210BCR/ABL oncogene in normal CD34+ cells.展开更多
Chronic myeloid leukemia(CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes(neutrophils, eosinophils, and basophils) and their precu...Chronic myeloid leukemia(CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes(neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia(Ph) chromosome or t(9;22) translocation(BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors(TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish(Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML.展开更多
文摘Objective： The authors used a meta-analytic technique to quantify the evidence of an association between ma- ternal alcohol consumption during pregnancy and childhood acute leukemia （AL）, which provided a basis for the prevention of childhood AL. Methods： Relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened. Subgroup meta-analysis was conducted according to the type of leukemia. Results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. Combined OR values and 95% CIs were statistically calculated with RevMan 4.2 software; Funnel plots were applied to conduct bias analysis for those included litera- tures. Results： Ten related literatures were included after data screening, 4593 cases in AL group and 6157 cases in control group respectively. According to heterogeneity test result （X2 = 16.26, P 〈 0.05）, the combined OR values and 95% CI were calculated with random effects model, which were 1.02 （0.92-1.14）, Z = 0.41, P = 0.68 〉 0.05, indicating that there was no significant difference between maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia （AL）. Subgroup analysis： for the association between maternal alcohol consumption during pregnancy and childhood acute lympho- blastic leukemia （ALL）, the combined OR value and 95% CI were 0.92 （0.84-1.00）, Z = 1.92, P = 0.05, indicating that there was significant difference between two groups; for the association between maternal alcohol consumption during pregnancy and childhood acute non-lymphoblastic leukemia （ANLL）, the combined OR values and 95% CI were 0.82 （0.61-1.11）, Z = 1.30, P = 0.19 〉 0.05, indicating that there was no significant difference between two groups. Conclusion： Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in childhood ANLL.
基金ThisstudywassupportedbyTianjinKeyProjectFund grant 99380 45 11
文摘Abstract:Objective To develop a primary human hematopoietic stem/progenitor cell model for chronic myeloid leukemia (CML) and study signal transduction and molecular regulation mechanisms in CML. Methods We developed a human model of p210BCR/ABL positive CML by transducing normal human umbilical cord blood CD34+ cells with a retroviral vector containing the b3a2 bcr/abl cDNA. We also examined whether this model recreated the cellular phenotype of CML by assessing cell adhesion, cell migration, cell proliferation and cell survival. Results We found that significantly more myeloid colony forming units grew from p210BCR/ABL expressing cells, adhesion of p210BCR/ABL expressing CD34+ cells to fibronectin was decreased but migration over fibronectin was enhanced compared with mock transduced CD34+ cells. In this model, we showed that the presence of p210BCR/ABL leads to elevated levels of p27kip in p210BCR/ABL expressing CD34+ cells. We also showed that multidrug resistance-1 (MDR-1) Pgp was upregulated in the p210BCR/ABL expressing cells which correlates with the expression of p210BCR/ABL. Conclusion This primary human CML model recreates most of the features of CML and provides a useful tool to study signal transduction and downstream molecular regulation drived by the p210BCR/ABL oncogene in normal CD34+ cells.
基金supported by National Natural Science Foundation of China (81270631)the National Natural Science Foundation of China for Overseas ChineseHong Kong and Macao Scholars Collaborated Researching Fund(31229003)
文摘Chronic myeloid leukemia(CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes(neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia(Ph) chromosome or t(9;22) translocation(BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors(TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish(Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML.
