Emerging Signatures of Hematological Malignancies from Gene Expression and Transcription Factor-Gene Regulations

Hematological malignancies are a diverse group of cancers developing in the peripheral blood, the bone marrow or the lymphatic system. Due to their heterogeneity, the identification of novel and advanced molecular signatures is essential for enhancing their characterization and facilitate its translation to new pharmaceutical solutions and eventually to clinical applications. In this study, we collected publicly available microarray data for more than five thousand subjects, across thirteen hematological malignancies. Using PANDA to estimate gene regulatory networks (GRNs), we performed hierarchical clustering and network analysis to explore transcription factor (TF) interactions and their implications on biological pathways. Our findings reveal distinct clustering patterns among leukemias and lymphomas, with notable differences in gene and TF expression profiles. Gene Set Enrichment Analysis (GSEA) identified 57 significantly enriched KEGG pathways, highlighting both common and unique biological processes across HMs. We also identified potential drug targets within these pathways, emphasizing the role of TFs such as CEBPB and NFE2L1 in disease pathophysiology. Our comprehensive analysis enhances the understanding of the molecular landscape of HMs and suggests new avenues for targeted therapeutic strategies. These findings also motivate the adoption of regulatory networks, combined with modern biotechnological possibilities, for insightful pan-cancer exploratory studies.