Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201.

Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201.
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对儿童常见急性淋巴细胞白血病的遗传易感性与 HLA-DPB1*0201 中的多态性肽结合袋谱相关。

DOI:
10.1093/hmg/11.14.1585
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发表时间:
2002
影响因子:
3.5
通讯作者:
U. Investigators
U. Investigators
中科院分区:
生物学2区
文献类型:
--
作者:
G. M. Taylor;S. Dearden;P. Ravetto;M. Ayres;P. Watson;A. Hussain;M. Greaves;F. Alexander;O. Eden;U. Investigators

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在以前的研究中,我们获得了一个小系列的患者(n = 63)的初步证据表明,儿童常见急性淋巴细胞白血病(c-ALL)的易感性与等位基因在HLA-DPB 1基因座,DPB 1 *0201。我们现在已经通过比较白血病儿童(n = 982)和两组非白血病儿童(一组由实体瘤儿童组成,不包括淋巴瘤(n = 409),另一组由正常婴儿组成(n = 864))的频率来测试这一假设。我们发现,与实体瘤儿童[c-ALL的比值比(OR),95%置信区间(CI):1.76,1.20-2.56; T-ALL:1.93,1.01-3.80]和正常婴儿相比,DPB 1 *0201分型的c-ALL和T-ALL儿童显著更多,而不是pro-B ALL或急性非ALL儿童(c-ALL的OR,95% CI:1.83,1.34-2.48; T-ALL:2.00,1.10-3.82)。在儿童c-ALL中,与实体瘤或正常婴儿相比,有更多的儿童分型为编码特定多态性氨基酸的DPB 1等位基因,这些氨基酸排列在DP β 1 *0201同种异型蛋白的抗原结合位点上,这表明儿童c-ALL的易感性可能受到DP β 1 *0201和其他DP β 1同种异型共有的DP β ABS氨基酸多态性的影响。这些结果指出了c-ALL易感性的机制,其涉及通过DP β 1 *0201相关同种异型蛋白呈递可能来自感染因子的特异性抗原肽,导致辅助性T细胞活化,介导白血病前细胞的增殖应激。
In a previous study, we obtained preliminary evidence in a small series of patients (n = 63) suggesting that susceptibility to childhood common acute lymphoblastic leukaemia (c-ALL) was associated with an allele at the HLA-DPB1 locus, DPB1*0201. We have now tested this hypothesis by comparing the frequency of children with leukaemia (n = 982) who typed for specific DPB1 alleles and two groups of non-leukaemic children, one consisting of children with solid tumours, excluding lymphomas (n = 409), the other consisting of normal infants (n = 864). We found that significantly more children with c-ALL and T-ALL, but not pro-B ALL or acute non-ALL typed for DPB1*0201 as compared with children with solid tumours [odds ratio (OR), 95% confidence interval (CI) for c-ALL: 1.76, 1.20-2.56; T-ALL: 1.93, 1.01-3.80] and normal infants (OR, 95% CI for c-ALL: 1.83, 1.34-2.48; T-ALL: 2.00, 1.10-3.82). In childhood c-ALL, significantly more children than those with solid tumours or normal infants typed for DPB1 alleles coding specific polymorphic amino acids lining the antigen-binding site of the DPbeta1*0201 allotypic protein, suggesting that susceptibility to childhood c-ALL may be influenced by DPbeta ABS amino acid polymorphisms shared by DPbeta1*0201 and other DPbeta1 allotypes. These results point to a mechanism of c-ALL susceptibility that involves the presentation of specific antigenic peptides, possibly derived from infectious agents, by DPbeta1*0201-related allotypic proteins, leading to the activation of helper T cells mediating proliferative stress on preleukaemic cells.
DOI: --
发表时间: 1994
期刊: Leukemia
影响因子: 11.4
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DOI: --
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期刊: Journal of immunology (Baltimore, Md. : 1950)
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DOI: 10.1016/s1201-9712(98)90116-3
发表时间: 1998
期刊: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
影响因子: --
作者:
Hayney,MS;Poland,GA;Jacobson,RM;Rabe,D;Schaid,DJ;Jacobsen,SJ;Lipsky,JJ
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发表时间: 1992-01
影响因子: 4.4
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