| RRC ID |
44515
|
| Author |
Patel V, Chen LS, Wierda WG, Balakrishnan K, Gandhi V.
|
| Title |
Impact of bone marrow stromal cells on Bcl-2 family members in chronic lymphocytic leukemia.
|
| Journal |
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.
|
| Volume |
55(4)
|
| Pages |
899-910
|
| Published |
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
|
| Times Cited |
14
|
|
WOS Category
|
ONCOLOGY
HEMATOLOGY
|
| Resource |
| Human and Animal Cells |
StromaNKtert(RCB2350) |
