Leukemia & lymphoma
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Leukemia & lymphoma · Mar 2009
ReviewOverexpression of the Fas-inhibitory molecule TOSO: a novel antiapoptotic factor in chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is characterised by resistance to apoptotic stimuli, mediated by overexpression of anti-apoptotic factors or extracellular survival signals. In this context, TOSO, also known as Fas-inhibitory molecule 3, was identified as a candidate gene over-expressed in CLL. TOSO is a transmembrane protein that inhibits Fas-mediated apoptosis by binding Fas-associated death domain via its C-terminal intracellular domain. ⋯ Both the association with unmutated IgV(H) gene status and the specific induction of TOSO via the BCR suggest autoreactive BCR signalling involving TOSO as a mediator of resistance to apoptosis in CLL. Further studies will reveal the functional context of TOSO in CLL and B cell biology. Surface expression of TOSO will enable antibody-based targeting of this novel CLL-antigen.