Figure 2.
Bone marrow MSPCs from AML patients harbor a distinct gene expression profile. (A) Principal component (PC) analysis of MSPCs isolated from AML patients and non-leukemic donors. (B) Hierarchical cluster analysis of genes with significantly different expression between MSPCs from AML patients (n = 8) and controls (n = 3) by the unweighted pair-group method with arithmetic averages. Gene signal intensities were normalized to the mean signal of all samples with log10 transformation. Horizontal rows represent individual samples; vertical columns represent individual genes. Black indicates average signal intensity, brightest red represents twofold or higher upregulated, and brightest blue represents twofold or lower downregulated gene expression relative to the mean. (C) Twenty top altered canonical pathways (P < .05) in bone marrow MSPCs from AML patients compared with controls were generated by Ingenuity Pathway Analysis (IPA) software (QIAGEN) and subcategorized into 4 functional groups. (D) Overlapping canonical pathway analysis generated by IPA. Black line indicates 4 genes and red line indicates more than 4 genes were shared between connected pathways. (E) Gene set enrichment analysis (GSEA) of proliferation-related gene sets with normalized enrichment score (NES) >1.5 and P < .05. (F) GSEA of osteogenesis-related gene sets with NES >1.5 and P < .05. (G) Left: heatmap of HSC-regulating genes in MSPCs from AML patients and controls. Gene signal intensities were central to the mean signal of individual gene symbols. Horizontal rows represent individual samples; vertical columns represent individual genes. Black indicates average signal intensity, brightest red represents 1.5-fold or higher upregulated, and brightest blue represents twofold or higher downregulated gene expression relative to the mean. Right: complete blood count of peripheral blood from corresponding patients at diagnosis including hemoglobin (Hb), absolute neutrophil count (ANC), and platelet (Plt). *P < .05 (determined by unpaired Student t test).