Targeting primary human leukaemia cells with RNA interference: Bcr‐Abl targeting inhibits myeloid progenitor self‐renewal in chronic myeloid leukaemia cells

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Summary: We have investigated functional outcome of challenging primary chronic myeloid leukaemia (CML) cells with Bcr‐Abl fusion sequence‐directed RNA interference (RNAi). We targeted the Bcr‐Abl b3a2 variant, by RNAi, in primary chronic phase CML cells, and detected strikingly reduced proliferation of myeloid precursor cells expressing this variant. Lack of an effect in cells expressing a distinct Bcr‐Abl variant confirmed the specificity of the response. Through the functional targeting of an oncogene in primary human tumour cells, we have demonstrated that Bcr‐Abl enhances CML progenitor cell amplification, and that RNAi may be suitable for development as a specific anti‐leukaemia treatment.

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