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BIK (Bcl2-Interacting Killer) CpG methylation in multiple myeloma: a potential predictor of relapsed/refractory disease with therapeutic implications.
MedLine Citation:
PMID:  22288719     Owner:  NLM     Status:  Publisher    
Abstract BIK (bcl2-interacting killer) is the founding member of the BH3-only BCL-2 family of pro-apoptotic proteins, which is found suppressed in various cancers. In multiple myeloma (MM), BIK has been shown to be epigenetically silenced in vitro but there is lack of clinical data. We investigated CpG methylation status of BIK promoter in a well-characterized clinical series of multiple myeloma (MM) patients and analyzed for clinical relevance. Forty MM patients (21 male, 19 female, mean age 66) were studied. According to International Staging System (ISS) there were classified to stage-I 16 patients, stage-II 12 patients and stage-III 12 patients. Methylation in the BIK CpG island was assessed by methylation-specific PCR (MSP) assay. Logistic regression analysis was used to investigate for associations between gene methylation and age, ISS stage, performance status, extramedullary disease, bone disease, anemia (Hb10<mg/dl), serum albumin, beta 2 microglobulin levels and relapsed/refractory disease. Methylation in the BIK CpG Island was detected in 16 patients (40%) with a trend favouring male gender (OR=3.08, p=0.09) and the development of bone disease and extramedullary disease (OR=1.6, p=0.35 and OR=3, p=0.14 respectively). MM patients with methylated the BIK CpG island had a statistically significant risk for evolving into relapsed/refractory disease (OR=5.4, p=0.03). This study provides clinical evidence that methylation-induced transcriptional silencing of BIK pro-apoptotic gene may occur in MM, which might serve as a predictor of developing relapsed/refractory MM. These findings warrant validation in larger cohorts of patients and suggest therapeutic utility for agents that enhance BIK expression.
Eleftheria Hatzimichael; Aggeliki Dasoula; Valentinos Kounnis; Leonidas Benetatos; Aggeliki Dasoula; Cristiana Lo Nigro; Laura Lattanzio; Alexandra Papoudou-Bai; George Dranitsaris; Evangelos Briasoulis; Tim Crook
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-30
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  -     ISSN:  1029-2403     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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