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The progression of chronic myelogenous leukemia (CML) to blast crisis is supported by self-renewing leukemic stem cells. In normal mouse hematopoietic stem cells, the process of self-renewal involves the β-catenin–signaling pathway. We investigated whether leukemic stem cells in CML also use the β-catenin pathway for self-renewal.

We used fluorescence-activated cell sorting to isolate hematopoietic stem cells, common myeloid progenitors, granulocyte–macrophage progenitors, and megakaryocyte–erythroid progenitors from marrow during several phases of CML and from normal marrow. BCR-ABL, β-catenin, and LEF-1 transcripts were compared by means of a quantitative reverse-transcriptase–polymerase-chain-reaction assay in normal and CML hematopoietic stem cells and granulocyte–macrophage progenitors. Confocal fluorescence microscopy and a lymphoid enhancer factor …