title: Impact of bone marrow stromal cells on Bcl-2 family members in chronic lymphocytic leukemia.
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.
authors.affiliation: Department of Experimental Therapeutics.
authors.forename: Viralkumar
authors.initials: V
authors.lastname: Patel
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Chen
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Kumudha
authors.initials: K
authors.lastname: Balakrishnan
authors.forename: Varsha
authors.initials: V
authors.lastname: Gandhi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger