Claire L Dallman

Publications (3)17.61 Total impact

• Article: Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to a cell death molecule by efficient caspase-mediated cleavage.

  Jorg Michels, Jason W O'Neill, Claire L Dallman, Amalia Mouzakiti, Fay Habens, Matthew Brimmell, Kam Y J Zhang, Ruth W Craig, Eric G Marcusson, Peter W M Johnson, Graham Packham
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  ABSTRACT: Enforced expression of the antiapoptotic Bcl-2 family protein Mcl-1 promotes lymphomagenesis in the mouse; however, the functional role of Mcl-1 in human B-cell lymphoma remains unclear. We demonstrate that Mcl-1 is widely expressed in malignant B-cells, and high-level expression of Mcl-1 is required for B-lymphoma cell survival, since transfection of Mcl-1-specific antisense oligodeoxynucleotides was sufficient to promote apoptosis in Akata6 lymphoma cells. Mcl-1 was efficiently cleaved by caspases at evolutionarily conserved aspartic acid residues in vitro, and during cisplatin-induced apoptosis in B-lymphoma cell lines and spontaneous apoptosis of primary malignant B-cells. Overexpression of the Mcl-1 cleavage product that accumulated during apoptosis was sufficient to kill cells. Therefore, Mcl-1 is an essential survival molecule for B-lymphoma cells and is cleaved by caspases to a death-promoting molecule during apoptosis. In contrast to Mcl-1, Bcl-2 and Bcl-XL were relatively resistant to caspase cleavage in vitro and in intact cells. Interfering with Mcl-1 function appears to be an effective means of inducing apoptosis in Mcl-1-positive B-cell lymphoma, and the unique sensitivity of Mcl-1 to caspase-mediated cleavage suggests an attractive strategy for converting it to a proapoptotic molecule.
  Oncogene 07/2004; 23(28):4818-27. · 6.37 Impact Factor
• Article: Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to a cell death molecule by efficient caspase-mediated cleavage

  Jorg Michels, Jason W O'Neill, Claire L Dallman, Amalia Mouzakiti, Fay Habens, Matthew Brimmell, Kam YJ Zhang, Ruth W Craig, Eric G Marcusson, Peter WM Johnson, Graham Packham
  [show abstract] [hide abstract]
  ABSTRACT: Enforced expression of the antiapoptotic Bcl-2 family protein Mcl-1 promotes lymphomagenesis in the mouse; however, the functional role of Mcl-1 in human B-cell lymphoma remains unclear. We demonstrate that Mcl-1 is widely expressed in malignant B-cells, and high-level expression of Mcl-1 is required for B-lymphoma cell survival, since transfection of Mcl-1-specific antisense oligodeoxynucleotides was sufficient to promote apoptosis in Akata6 lymphoma cells. Mcl-1 was efficiently cleaved by caspases at evolutionarily conserved aspartic acid residues in vitro, and during cisplatin-induced apoptosis in B-lymphoma cell lines and spontaneous apoptosis of primary malignant B-cells. Overexpression of the Mcl-1 cleavage product that accumulated during apoptosis was sufficient to kill cells. Therefore, Mcl-1 is an essential survival molecule for B-lymphoma cells and is cleaved by caspases to a death-promoting molecule during apoptosis. In contrast to Mcl-1, Bcl-2 and Bcl-XL were relatively resistant to caspase cleavage in vitro and in intact cells. Interfering with Mcl-1 function appears to be an effective means of inducing apoptosis in Mcl-1-positive B-cell lymphoma, and the unique sensitivity of Mcl-1 to caspase-mediated cleavage suggests an attractive strategy for converting it to a proapoptotic molecule.Keywords: apoptosis, Mcl-1, antisense, non-Hodgkin's lymphoma, Bcl-2, caspase
  Oncogene 05/2004; 23(28):4818-4827. · 6.37 Impact Factor
• Article: Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells.

  Sara M E Osford, Claire L Dallman, Peter W M Johnson, A Ganesan, Graham Packham
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  ABSTRACT: Apoptosis (or programmed cell death) is a genetically controlled "cell suicide" pathway which plays an essential role in deleting excess, unwanted or damaged cells during development and tissue homeostasis. Dysregulation of apoptosis contributes to a wide variety of pathological conditions, including AIDS, cardiovascular disease, infectious disease, autoimmunity and neurodegenerative disorders. Resistance to apoptosis is also a common feature in human malignancies, contributing to both the development of cancer and resistance to conventional therapies such as radiation and cytotoxic drugs, which function by activating apoptotic cell death pathways. Bcl-2 is one of the best characterized cell death control proteins; its overexpression confers resistance to a broad range of apoptosis inducers and the cell survival functions of Bcl-2 are activated by translocation in lymphomas and overexpression in many other cancer types. A wealth of experimental data supports the idea that Bcl-2 is an attractive and tractable target for newer molecularly directed anti-cancer strategies, designed to promote cancer cell death. Here we review current understanding of the mechanism of action and importance of Bcl-2 in cancer cells and progress in developing new agents to target this key survival molecule.
  Current Medicinal Chemistry 05/2004; 11(8):1031-9. · 4.86 Impact Factor