RRC ID 44515
著者 Patel V, Chen LS, Wierda WG, Balakrishnan K, Gandhi V.
タイトル Impact of bone marrow stromal cells on Bcl-2 family members in chronic lymphocytic leukemia.
ジャーナル Leuk Lymphoma
Abstract Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. High levels of Bcl-2 family anti-apoptotic proteins are responsible for apoptosis resistance. Besides anti-apoptotic proteins, the microenvironment provides substantial survival signals to CLL leukemic cells. However, in-depth knowledge on the role of individual Bcl-2 family members in the context of the microenvironment is still limited. We performed a comprehensive analysis of transcripts and proteins of 18 Bcl-2 family members using an "apoptosis array microfluidic card" in primary cells before and after stromal co-cultures. Our data showed that five of six anti-apoptotic members (excluding Bcl-b), two of three pro-apoptotic members (excluding Bok) and six of nine BH3-only members were present at detectable mRNA levels in CLL cells. Importantly, stromal-mediated extended survival of CLL cells was strongly associated with elevated global transcription. Upon co-culturing with stromal cells, there was an early response of an increase in anti- (2/5) and pro-apoptotic protein (3/8) transcripts on day 1, while an increase in anti-apoptotic proteins was observed on day 3, with no significant change in pro-apoptotic proteins. Our study revealed a differential pattern of expression of both transcripts and proteins following stromal co-cultures, proposing a significance of Bcl-2 family members in the stromal microenvironment.
巻・号 55(4)
ページ 899-910
公開日 2014-4-1
DOI 10.3109/10428194.2013.819573
PMID 23837491
PMC PMC4172382
MeSH Apoptosis / genetics Cell Survival Coculture Techniques Gene Expression Profiling Humans Leukemia, Lymphocytic, Chronic, B-Cell / genetics* Leukemia, Lymphocytic, Chronic, B-Cell / metabolism Mesenchymal Stem Cells / metabolism* Proto-Oncogene Proteins c-bcl-2 / genetics* Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Messenger / genetics Transcription, Genetic
IF 2.969
引用数 14
WOS 分野 ONCOLOGY HEMATOLOGY
リソース情報
ヒト・動物細胞 StromaNKtert(RCB2350)