Mutation affecting cell signalling in chronic lymphocytic leukemia identified

To gain a better understanding of the development of chronic lymphocytic leukemia, researchers at SciLifeLab/Uppsala University have studied a specific signalling pathway that affects the growth of tumour B-cells. They identified a signalling protein that was frequently mutated in more aggressive subsets of the disease. This mutation was also detected in other B-cell malignancies, thereby suggesting that a common mechanism may contribute to the growth and survival of tumour cells in these diseases.


In tumour cells, the signals controlling cell growth and survival are dysfunctional, thus enabling the cells to grow in an uncontrolled manner. In chronic lymphocytic leukemia (CLL) it is B-cells, a type of white blood cells, that proliferate out of control. In CLL and other B-cell malignancies researchers have previously observed that deregulation of the NF kappa B (NF-kB) signalling pathway appears to be particularly important. However, the genetic alterations behind this deregulated signalling have remained unknown.

Several research groups at Uppsala University participated in the present study, where they analysed the NF-kB genes in a large number of CLL patients. This analysis led to the identification of recurrent mutations in a specific gene, called NFKBIE, which encodes a protein involved in the NF-kB signalling pathway.

“The most common mutation was a small deletion within the NFKBIE gene. This results in the production of a non-functional protein, which ultimately affects NF-kB signalling. Since the dysfunctional protein, IkBe, normally functions as an inhibitor, the mutation leads to activated signalling compared to the normal situation”, says SciLifeLab faculty member Richard Rosenquist who led the study.

The results have been published in the Journal of Experimental Medicine

Read the publication in Journal of Experimental Medicine

Read the full news article at Uppsala University


Last updated: 2015-05-20

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