Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations

The resistance of CML leukemic stem cells (LSC) to tyrosine kinase inhibitor therapies targeting BCR-ABL leads to persistence of disease in most cases. We have identified novel putative therapeutic targets that are differentially expressed in CML LSCs compared to normal hematopoietic stem cells (HSC) by transciptional profiling of stem and progenitor cell populations from CML patients and normal donors. These data are used to obtain 97 genes that are differentially expressed in CML vs. normal stem and progenitor cells and 236 transcripts that show evidence of alternative exon usage in CML vs. normal stem cells. Bone marrow stem and progenitor cell fractions from 5 patients with newly diagnosed and untreated chronic phase CML and 5 healthy donors were analyzed. Contrasts between CML vs. normal stem and progenitors overall and CML vs. normal stem cells were performed using Partek Genomic Suite software. Genes with |log2(fold-change) > 1| and false discovery rate (FDR) of 0.05 were identified as significantly differentially expressed. To identify genes with evidence of alternative exon useage, contrasts between CML and normal stem cell populations were performed, and genes with an alternative splicing FDR of 0.01 were considered to be alternatively spliced.