Determining the key genes and cellular signaling pathways involved in the pathogenesis and development of aggressive types of adult leukemia/lymphoma derived from T (ATLL) cells

Adult T-cell leukemia/lymphoma (ATLL) is a cancer with a very poor prognosis. ATLL has four subgroups, acute, chronic, lymphoma, and smoldering, with very different prognoses. In this study, we tried to better understand the pathogenesis of ATLL and the differences between its subgroups by using gene expression data and bioinformatics methods.

Genes with altered expression were identified among different types of ATLL. In order to determine the key genes, the network of protein interactions between the resulting genes was constructed. After screening the hub genes based on the network centrality indices, the cell signaling pathways related to them were identified.

Comparing the acute type with the chronic and silent types, the cell signaling pathways involved in regulating the function of the immune system are expressed differently. In comparison of acute and chronic type with healthy people, genes related to malignancy are involved. In comparing the silenced type with healthy individuals, the pathways related to infections are disrupted. In the secondary comparison, it was found that the genes related to cell proliferation and malignancy in the acute form were expressed more and the genes related to the immune system were less expressed in these patients than in the rest of the population.

It seems that manipulations by the virus resulting in immune escape and also in increased proliferation of infected cells have a decisive role in the occurrence of the aggressive type of the disease. Further investigations can lead to the development of new diagnostic methods, determining prognosis and even the detection of targets for gene therapy.