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The Genesis Of Acute Lymphoblastic Leukemia, EBV Infection And BCR/ABL Fusion Gene Expression Associated With The Polymorphisms Of IL-10 Promoter Gene

Posted on:2011-06-09Degree:MasterType:Thesis
Country:ChinaCandidate:C WangFull Text:PDF
GTID:2154360308474474Subject:Internal Medicine
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Objection: EBV (Epstein-barr virus) infection is more common in lymphocytic system tumors, and is related to the genesis, development and prognosis of lymphocytic system tumors. Products of BCRF1 reading frame of EBV has 84% homology in amino acid sequence with human IL-10and has a similar immuno-suppressive effect as human IL-10. EBV has a synergistic effect with IL-10 in tumor genesis. Tumor cells can secrete IL-10. Cancer patients having high level of IL-10 often have poor prognosis. Secretion of IL-10 by tumor cells can be affected by the single nucleotide polymorphisms in the promoter region of IL-10 gene. The purpose of the present study is to evaluate whether the polymorphisms of IL-10 gene can affect the genesis of acute lymphoblastic leukemia, EBV infection and the expression of BCR / ABL fusion gene.Materials and Methods: Restriction fragment length polymorphisms was detected in the promoter region -819C/T, -592A/C of IL-10 gene in 323 cases of cord blood, 115 patients with acute lymphoblastic leukemia. Sequencing was done in part of these samples to confirm the results. Real-time quantitative polymerase chain reaction was performed to detect the EBV infection in 42 patients with ALL and the expression of BCR/ABL fusion gene in 36 cases with ALL.χ2 test and Fisher exact test was done for statistical analysis.Results: The number (percentage) of -819CC, TT, CT genotypes and C,T allegenes freqencies in umbilical cord blood samples are 32(9.9%), 53(16.4%),238(73.7%), 302(46.7%) ,344(53.3%),-592AA, CC, AC genotypes and A,C freqencies are 38(11.8%),50(15.5%),235(72.8%), 311(48.1%) 335(51.9%)。The number of -819CC, TT, CT genotypes and C,T allegenes freqencies in acute lymphoblastic leukemia group are 17(14.8%),52(45.2%),46(40%)and 80(34.8%) 150(65.2%), respectively, -592AA, CC, AC genotypes and A,C freqencies are 50(43.5%),19(16.5%),46(40%)and 146(63.5%)and 84(36.5%), respectively。It is clear that -819TT and -592AA genotype are more frequency in ALL group comparing to that in umbilical cord blood group (45.2%VS 16.4% and 43.5%vs11.8%). -819T and -592A allegenes are also more frequency in ALL group comparing to the umbilical cord blood group, although statistic analysis result showed that P value is smaller than 0.05.The number (percentage) of -819CC, TT, CT genotypes and C, T allegenes freqencies in EBV+ ALL group are 2(9.1%),9(40.9%),11(50%)and 15(34.1%) ,29(65.9%), respectively, -592AA, CC, AC genotypes and A,C allegenes frequencies are 7(31.8%),3(13.6%),12(54.5%), 26(59.1%)18(40.9%)。The number (percentage) of -819CC, TT, CT genotypes and C,T allegenes freqencies in EBV-ALL group are 7(35.0%),9(45.0%),4(20.0%), 18(45.0%) 22(55.0%);and -592AA, CC, AC genotypes and A,C allegenes frequencies are 9(45.0%),7(35.0%),4(20.0%), 22(55.0%)18(45.0%)。Though there are no statistically significant difference in the number and percentage of each genotype between the two groups(P>0.05), a tendency can be seen that -819CC and -592CC genotypes were more frequency in EBV-ALL group comparing to that in the EBV+ALL group (35.0%vs9.1%and 35.0%vs13.6%).The same phenomenon was seen in BCR/ABL+ALL and BCR/ABL-ALL groups. The number (percentage) of -819CC, TT, CT genotypes and C,T allegenes frequencies in BCR/ABL+ALL group are 0(0.0%),9(45.0%),11(55.0%), 11(27.5%) and 29(72.5%), respectively;and -592AA, CC, AC genotypes and A,C allegene frequencies are 9(45.0%),1(5.0%),10(50.0%), 28(70.0%)12(30.0%)。The number (percentage) of -819CC, TT, CT genotypes and C,T allegene frequencies in BCR/ABL-ALL group are 3(18.8 %) ,8(50.0%),5(31.3%), 11(34.4%) 21(65.6%);-592AA, CC, AC genotypes and A,C allegene frequencies are 8(50.0%),3(18.8%),5(31.3%), 21(65.6%) 11(34.4%)。Though there is no statistically significant difference in the two groups(P>0.05), A tendency can be seen that -819CC,-592CC are more frequency in BCR/ABL-ALL group comparing to that in BCR/ ABL+ ALL group (18.8%vs0.0%and18.8%vs5.0%).Conclusion: The polymorphisms of -819T,-592A of IL-10 gene may be associated with the susceptibility to acute lymphoblastic leukemia. IL-10 -819CC, -592CC may protect ALL patients from EBV infection, and ALL patients with -819CC, -592CC genotype have low tendency with BCR/ABL expression. However, for confirming these conclusions, further studies with more samples are needed to be done.
Keywords/Search Tags:Acute lymphoblastic leukemia, Epstein-Barr virus, IL-10 single nucleotide polymorphisms
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