The importance of a sub-region on chromosome 19q13.3for prognosis of multiple myeloma patients after high-dosetreatment and stem cell support: a linkage disequilibriummapping in RAI and CD3EAP
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Annette J. Vangsted & Tobias Wirenfeldt Klausen &Peter Gimsing & Niels Abildgaard & Niels F. Andersen &Henrik Gregersen & Bjّrn Andersen Nexّ &Ulla Bi
- چاپ و سال / کشور: 2010
Description
The gene RAI was originally described as an inhibitor of RelA/p65 subunit of nuclear factor ƒبB (NF.ƒبB). Here, we analyse the association between genetic variation in the genes RAI and CD3EAP and outcome of 348 myeloma patients treated with high-dose treatment (HDT), 146 patients treated with interferon-ƒ؟ (INF-ƒ؟) as maintenance treatment, 177 patients treated with thalidomide, and 74 patients treated with bortezomib at relapse and address if the effects of polymorphisms in CD3EAP and RAI are modified by a functional polymorphism in NF„KB1. By linkage disequilibrium mapping, we found that variant alleles of several polymorphisms in a sub-region of 19q13.3 spanning the regions RAI-intron1-1 to RAI intron1- 3 and the region exon1 to exon3.6 in CD3EAP were associated with prolonged time-to-treatment failure (TTF; p=0.003) and overall survival (analyses revealed that none of the haplotypes were more strongly associated to TTF or OS than the two strongly linked SNPs, RAI-intron1-1 (rs4572514) and CD3EAP G- 21A (rs967591). The association of RAI-intron1-1 and CD3EAP G-21A with TTF was independent of NFKB1-94 ins/del, but homozygous ins-allele carriers which were also variant allele carriers of RAI-intron1-1 or CD3EAP G- 21A had the longest OS. Among patients treated with INF- ل or thalidomide, no effect was seen in relation to genotype. Our results indicate that polymorphism in RAI and CD3EAP are associated with outcome of myeloma patients treated with HDT. Combination analyses with the functional polymorphism in NFKB1 suggest that a possibly functional effect of RAI or CD3EAP could be related to NF–êB
Ann Hematol (2011) 90:675–684 DOI 10.1007/s00277-010-1105-z Received: 4 September 2010 / Accepted: 9 October 2010 / Published online: 3 November 2010
