TY - JOUR
T1 - Strategy to induce apoptosis and circumvent resistance in chronic lymphocytic leukaemia
AU - Chen, Rong
AU - Plunkett, William
N1 - Funding Information:
W. Plunkett received research funding from Sunesis Pharmaceuticals. R. Chen discloses no conflict of interest.
Funding Information:
This study was supported in part by the CLL Global Research Foundation and by grant CA81534 , from the National Cancer Institute, Department of Health and Human Services.
PY - 2010/3
Y1 - 2010/3
N2 - Chronic lymphocytic leukaemia (CLL) is characterised by the dependence on the overexpression of anti-apoptotic proteins to maintain their survival. Based on this biological context, a strategy for CLL therapy was proposed using inhibitors of transcription and translation to transiently reduce the short-lived survival proteins and induce cell death. This includes inhibitors of the cyclin-dependent kinases required for the activation of RNA polymerase II, as well as homoharringtonine and silvestrol, the natural compounds that inhibit translation. As their actions are independent of p53 or ataxia telangiectasia mutated (ATM) function, agents that act by such mechanisms are promising to overcome resistance to current CLL therapy. Further, the combination of inhibitors of transcription and translation, together with other approaches that interfere with the function of anti-apoptotic proteins, may initiate synergistic killing in CLL.
AB - Chronic lymphocytic leukaemia (CLL) is characterised by the dependence on the overexpression of anti-apoptotic proteins to maintain their survival. Based on this biological context, a strategy for CLL therapy was proposed using inhibitors of transcription and translation to transiently reduce the short-lived survival proteins and induce cell death. This includes inhibitors of the cyclin-dependent kinases required for the activation of RNA polymerase II, as well as homoharringtonine and silvestrol, the natural compounds that inhibit translation. As their actions are independent of p53 or ataxia telangiectasia mutated (ATM) function, agents that act by such mechanisms are promising to overcome resistance to current CLL therapy. Further, the combination of inhibitors of transcription and translation, together with other approaches that interfere with the function of anti-apoptotic proteins, may initiate synergistic killing in CLL.
KW - anti-apoptotic proteins
KW - chronic lymphocytic leukaemia
KW - cyclin-dependent kinase
KW - therapy
KW - transcription inhibitor
KW - translation inhibitor
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U2 - 10.1016/j.beha.2010.01.003
DO - 10.1016/j.beha.2010.01.003
M3 - Review article
C2 - 20620979
AN - SCOPUS:77955752225
SN - 1521-6926
VL - 23
SP - 155
EP - 166
JO - Best Practice and Research: Clinical Haematology
JF - Best Practice and Research: Clinical Haematology
IS - 1
ER -