TY - JOUR
T1 - Impact of bone marrow stromal cells on Bcl-2 family members in chronic lymphocytic leukemia
AU - Patel, Viralkumar
AU - Chen, Lisa S.
AU - Wierda, William G.
AU - Balakrishnan, Kumudha
AU - Gandhi, Varsha
N1 - Funding Information:
This work was supported in part by grants from the CLL Consortium (PO1CA081534, to V. G. and W. G. W), the CLL-Global Research Foundation (to K. B.) and a Cancer Center Support Grant, P30-16672, from the National Cancer Institute.
PY - 2014/4
Y1 - 2014/4
N2 - 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, stromalmediated 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.
AB - 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, stromalmediated 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.
KW - Apoptosis
KW - Bcl-2 family members
KW - Chronic lymphocytic leukemia
KW - MRNA
KW - Microarray
KW - Microenvironment
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U2 - 10.3109/10428194.2013.819573
DO - 10.3109/10428194.2013.819573
M3 - Article
C2 - 23837491
AN - SCOPUS:84904355799
SN - 1042-8194
VL - 55
SP - 899
EP - 910
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 4
ER -