Community Research and Development Information Service - CORDIS


ART Report Summary

Project ID: 617340
Funded under: FP7-IDEAS-ERC
Country: Belgium

Mid-Term Report Summary - ART (Aberrant RNA degradation in T-cell leukemia)

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature thymocytes that is caused the by the accumulation of several mutations and chromosomal defects. Central to the pathogenesis of T-ALL is the presence of activating NOTCH1 mutations and chromosomal rearrangements leading to the aberrant overexpression of TAL, TLX, HOXA or NKX transcription factor family members. We recently discovered mutations in genes encoding proteins implicated in RNA degradation in T-ALL, with loss-of-function mutations in the CNOT3 gene as the most frequent mutations. We have used the fruitfly as a model organism to study how loss of Not3 (the homolog of CNOT3 in fruitfly) is causing tumor formation in the fly. Our data show that the entire complex in which Not3 is functioning is important for tumor suppression and we identify control of DNA replication and the cell cycle as critical functions of the NOT3 complex. Studies in the mouse are ongoing to determine how these insights from the fruitfly can help us understand how mutations in CNOT3 can contribute to leukemia development.

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