| Chronic eosinophilic leukemia with erythroblastic proliferation and the rare translocation t(8;9)(p22;p24) with PCM1-JAK2 fusion gene - a distinct clinical, pathological and genetic entity with potential treatment target? | |
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MedLine Citation:
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PMID: 22288769 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Monika Prochorec-Sobieszek; Barbara Nasilowska-Adamska; Katarzyna Borg; Izabella Kopeć; Kinga Kos-Zakrzewska; Przemyslaw Juszczyński; Krzysztof Warzocha |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-30 |
Journal Detail:
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Title: Leukemia & lymphoma Volume: - ISSN: 1029-2403 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9007422 Medline TA: Leuk Lymphoma Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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