NOTCH1 Signalling: A key pathway for the development of high-risk chronic lymphocytic leukaemia.

ABSTRACT: NOTCH1 is a cell surface receptor that releases its intracellular domain as transcription factor upon activation. With the advent of next-generation sequencing, the NOTCH1 gene was found recurrently mutated in chronic lymphocytic leukaemia (CLL). Here, virtually all NOTCH1 mutations affect the protein's PEST-domain and impair inactivation and degradation of the released transcription factor, thus increasing NOTCH1 signalling strength. Besides sequence alterations directly affecting the NOTCH1 gene, multiple other genomic and non-genomic alterations have by now been identified in CLL cells that could promote an abnormally strong NOTCH1 signalling strength. This renders NOTCH1 one of the key signalling pathways in CLL pathophysiology. The frequency of genomic alterations

SUBMITTER: Edelmann J 

PROVIDER: S-EPMC9606825 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature