Interaction between BCL2 and Interleukin-10 Gene Polymorphisms Alter Outcomes of Diffuse Large B-Cell Lymphoma following Rituximab Plus CHOP Chemotherapy
Interaction between BCL2 and Interleukin-10 Gene Polymorphisms Alter Outcomes of Diffuse Large B-Cell Lymphoma following Rituximab Plus CHOP Chemotherapy
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DOI：
10.1158/1078-0432.ccr-08-1588
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发表时间：
2009-03-15
影响因子：
11.5
通讯作者：
Kim, Dong Hwan
中科院分区：
文献类型：
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作者：
Park, Yeon Hee;Sohn, Sang Kyun;Kim, Dong Hwan
目的：利妥昔单抗可能通过抑制白介素10(IL-10)介导的环路，从而下调bcl2的表达，从而克服bcl2介导的化疗耐药。我们研究了BCL2/IL10基因环遗传变异对CHOP或美罗华联合CHOP(R-CHOP)化疗方案治疗弥漫性大B细胞淋巴瘤疗效的影响。结果：IL10 SNPs、-819 TT/TC或-592 AA/AC等位基因与CHOP疗效相关(P=0.04)。IL-10单倍型与R-CHOP治疗后的无失败生存期(FFS)或进展(P=0.007)相关，而-938AA BCL2基因对总生存期有显著影响(P=0.04)。在同时具有-938 AA BCL2基因型和CC IL10单倍型1~2个拷贝的人群中，BCL2和IL10 SNPs的交互作用显著。结论：弥漫性大B细胞淋巴瘤的R-CHOP化疗耐药可能与bcl2和IL10基因的相互作用有关。
Purpose: Rituximab may overcome bcl-2-mediated chemoresistance through the inhibition of interleukin-10 (IL-10)-mediated loops, thus down-regulating bcl-2 expression. We examined the effects of genetic variation in BCL2/IL10 gene loops on treatment outcomes of diffuse large B-cell lymphoma when treated with either CHOP or rituximab plus CHOP (R-CHOP) chemotherapy.Experimental Design: Four genotypes were tested including BCL2 -938 C > A (rs2279115), +21 A > G (rs1801018), IL10 -819 T > C (rs1800871), and -592 A > C (rs1800872) in patients receiving either R-CHOP (n = 125) or CHOP (n = 110).Results: IL10 SNPs, -819 TT/TC or -592 AA/AC genotypes correlated with improved CHOP response rates (P = 0.04). Neither polymorphism separately influenced the failure-free survival (FFS) or overall survival in patients, but the IL10 haplotype was associated with treatment outcomes after R-CHOP for FFS (P = 0.03) or progression (P = 0.007), whereas the -938 AA BCL2 genotype significantly affected overall survival (P = 0.04). An interactive effect between BCL2 and IL10 SNPs was significant in the group with both -938 AA BCL2 genotype and 1 to 2 copies of CC IL10 haplotype. This group showed a better FFS (P = 0.01) and a lower probability of progression (P = 0.004) compared with other genotype groups when treated with R-CHOP chemotherapy.Conclusions: These data indicated that R-CHOP chemotherapy resistance in diffuse large B-cell lymphoma may involve interactions between the BCL2 and IL10 genes.