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. 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, and LB and CD34+ isolated from PB as experiment 4. Then, protein–protein interaction network of DEGs was constructed to identify critical genes. Regulatory impact factors were used to identify critical transcription factors from the differential co-expression network constructed via reanalyzing the microarray profile from the perspective of differential co-expression. Gene ontology enrichment was performed to extract biological meaning. The comparison among the number of DEGs obtained in four experiments showed that cells did not tend to differentiation and CD34+ was more similar to cancer stem cells. Based on the results of protein–protein interaction network, CREBBP, F2RL1, MCM2, and TP53 were respectively the key genes in experiments 1, 2, 3, and 4. From gene ontology analysis, we found that immune response was the most common one in four stages. Our results might provide a platform for determining the pathology and therapy of AML.