Similarity of regulatory network between leukaemia stem cells and normal hemopoietic stem cells

摘要

Few studies have deeply compared the expression profiles between normal hematopoietic cells and acute myeloid leukaemia (AML) blasts. To reveal the biology of AML, we compared gene expression profiles between normal hematopoietic cells from 38 healthy donors and leukemic blasts (LBs) from 26 AML patients. Normal hematopoietic samples included CD34+ selected cells, unselected bone marrows (BMs), and unselected peripheral bloods (PBs). Gene expression profiles of normal hematopoietic cells from healthy donors and LBs from AML patients were compared to identify differentially expressed genes (DEGs). We defined the comparison of LB and unselected BM as experiment 1, LB and CD34+ isolated from BM as experiment 2, LB and unselected PB as experiment 3, as well as LB and CD34+ isolated from PB as experiment 4. Then, protein-protein interaction (PPI) network of DEGs was constructed to identify critical genes. Regulatory impact factors (RIF) was used to identify critical transcription factors (TFs) from the differential co-expression network constructed via re-analyzing the microarray profile from the perspective of differential co-expression. GO (Gene Ontology) enrichment was performed to extract biological meaning. The comparison among the number of DEGs obtained in the four experiments showed LB cells did not tend to differentiation and CD34+ was more similar to cancer stem cells. Based on the results of PPI network, CREBBP，F2RL1, MCM2 and TP53 were respectively the key genes in experiment 1, 2, 3, and 4. For GO analysis, we found that immune response was the common one in these four stages. Our results might provide a platform for determining the pathology and therapy of AML.