The hypoxia-driven transcriptional response in CML progenitor cells is distinct from that elicited by imatinib. (A) Microarray heat maps show changes in gene expression for CP-CD34⁺ progenitors from 3 individuals (triplicate columns) after imatinib (+) or DMSO (−) control treatments in 0.5% or 21% O₂ for 24 or 96 hours. Color scale shows fold-change upregulation (red) or downregulation (green) of gene expression for each sample compared with their individual untreated controls (DMSO, 21% O₂) on a Log2 scale. The overall changes in gene expression for each treatment are shown as averages for all 3 patients (single columns). Yellow boxes demarcate target genes specifically induced by hypoxia, whereas blue boxes show similar transcriptional response for imatinib treatments with or without hypoxia. (B) Proportional Venn diagrams show unique and coregulated target genes induced by imatinib and/or hypoxia treatments after 24 or 96 hours. The number of differentially expressed genes is stated for each condition, and the corresponding percentage of the total number of genes for each time is denoted in parentheses. The box shows 14 survival genes consistently upregulated by hypoxia with and without imatinib at 24 and 96 hours. (C) Ingenuity Pathway Analysis of the upregulated (red) and downregulated (green) hypoxia subset target genes at 24 and 96 hours, respectively, showing the top 10 most significantly affected biological functions for each condition. Yellow lines indicate threshold cutoff of P < .05 for Fisher's exact test.