Ikaros is the founding member of a family of zinc finger DNA binding proteins expressed predominantly in haematopoietic cells. IKZF1, the gene encoding Ikaros, is mutated in over 80% of BCR-ABL1 B-progenitor acute lymphoblastic leukaemias (ALL). Ikaros acts as a tumour suppressor in pre-B cells by limiting the duration of pre-B cell receptor signalling and thereby restraining pre-B cell proliferation. The molecular details of this mechanism are the focus of a current LRF project grant. Interestingly, Ikaros also blocks cell cycle progression when ectopically expressed in non-lymphoid cells, suggesting the existence of additional, pre-B cell receptor independent pathways of cell cycle control by Ikaros. Here we propose to identify components of pre-B cell receptor independent pathways using a genome-wide screen based on RNA interference. The results will lead to a better understanding of Ikaros as a tumour suppressor and may lead to the identification of novel drug targets. The study is complementary to the current LRF project on the regulation of pre-B cell receptor expression and will greatly benefit from it.
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