The network structure of hematopoietic cancers

Abstract

Hematopoietic cancers (HCs) are a heterogeneous group of malignancies that affect blood, bone marrow and lymphatic system. Despite arising from derivatives of hematopoietic stem cells, each disease has a unique set of characterizing genomic irregularities. Gene co-expression networks (GCNs) have been useful to analyze and integrate information of cancer transcriptomes. Here, we explored the co-expression landscape in HC, by inferring GCNs from four hematopoietic cancers (B and T-cell acute leukemia, -BALL, TALL-, acute myeloid leukemia -AML- and multiple myeloma -MM-) as well as non-cancer bone marrow. We characterized their structure (topological features) and function (enrichment analyses). We found that, as in other types of cancer, the highest co-expression interactions are intra-chromosomal, which is not the case for control GCNs. We also detected a highly co-expressed group of overexpressed pseudogenes in HC networks. The four GCNs present only a small fraction of common interactions, related to canonical functions, like immune response or erythrocyte differentiation. Those genes are differentially expressed in a unique fashion for each HC. For instance, cell cycle-associated genes are underexpressed in MM and AML, slightly overexpressed in BALL but highly overexpressed in TALL. With this approach, we are able to reveal cancer-specific features useful for detection of disease manifestations.

Pseudogenes in Cancer: State of the Art

“…Although this phenomenon has been reported in various tissues, our recent study on the GCNs of hematopoietic cancer specifically examined the co-expression profile of pseudogenes in these cancer types [ 132 ]. Confirming the loss of inter-chromosomal regulation in hematopoietic cancers, we identified an increased proportion of interactions between pseudogenes, particularly those derived from housekeeping genes such as eukaryotic elongation factors and riboproteins.…”

“…The co-expression analysis of gene expression profiles is a valuable approach for detecting potential rewiring of normal circuits contributing to the regulatory programs of diseases. Future research focused on understanding the functions of pseudogenes, particularly those derived from housekeeping genes, could provide valuable information regarding the biological significance of increased pseudogene co-expression observed in cancer GCNs [ 132 ]. Such investigations hold the potential to enhance our understanding of pseudogenes and their role in cancer.…”