How to deal with "traitors"

The mechanisms associated with the transformation of B-lymphocytes into cancer cells have been studied

Anna Stavina, XX2 century

When B-lymphocytes (a type of white blood cells designed to fight diseases) are reborn into cancer cells, they become a problem, and now they should be dealt with. However, these "treacherous" B-lymphocytes are able to avoid death. Finding ways to destroy such cells is an important goal of cancer research.

Recently, scientists from the Technion – the Israel Institute of Technology – have identified the conditions necessary for the discovery of a biochemical pathway for the destruction of B-lymphocytes that have become malignant and have learned to avoid aggression from the immune system. The results of the work can be used to create new approaches to the treatment of leukemia and other oncological diseases associated with B-lymphocytes.

The results of the work were published in the journal Cell Reports (Coffre et al., miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation).

According to the researchers, the population of B-lymphocytes is normally regulated by two processes: positive selection (at the same time, cells multiply, but their survival is under control) and negative selection (in this case, the process of "cell death" is activated, preventing the aggression of lymphocytes against body tissues). The course of these processes in cancer cells changes, so that such cells can not only survive and grow, but also resist attempts to destroy.

"We have traced the mechanism by which the reborn B lymphocytes manage to avoid death," said the lead author of the study, doctoral student David Benhamou, who conducted the work under the supervision of Professor Doron Melamed, Professor of the Technion Faculty of Medicine. – The information obtained can help block the mechanism of positive selection that allows cancer cells to survive. We will also be able to fight such cells more effectively by activating negative selection" (see the press release of New Clues in Fight Against Leukemia, Other B Cell Cancers).

The mechanism by which the reborn B-lymphocytes survive and avoid death is quite complex. It involves microRNA molecules, Pten – a protein encoded by the PTEN gene (mutations in this gene play an important role in the development of many types of cancer), an important regulatory protein CD19 and the enzyme PI3K, known for its ability to protect cancer cells from "cell death".

Figure from an article in Cell Reports – VM

"The activity of the PI3K enzyme regulates the processes of positive and negative selection of B-lymphocytes," explained Professor Melamed. – It itself, in turn, is controlled by another biochemical process, in which the Pten protein plays an important role. Until recently, the role of the "negotiations" between the PI3K enzyme and the Pten protein was unclear, but our work demonstrated that the microRNA controlling gene expression and playing the role of "mediator" in these "negotiations" can trigger the process of transformation of B lymphocytes into cancer cells and enable them to avoid "cell death".

New data on the processes of regulating the activity of the PI3K signaling pathway and how this signaling pathway affects the fate of cancer cells can help in the treatment of leukemia using microRNAs. Thus, it will be possible either to trigger the mechanism of destruction of cancer cells, or to prevent the transformation of normal B-lymphocytes into malignant ones.

Portal "Eternal youth" http://vechnayamolodost.ru  24.11.2016