Global Shift in Alternative Splicing and Therapeutic Susceptibilities in Leukemia Driven by METTL3 Overexpression

Mutations in splicing factors are commonly observed in chronic lymphocytic leukemia (CLL); however, other mechanisms can also contribute to the dysregulation of alternative splicing. One example is the overexpression of the m 6 A RNA methyltransferase METTL3, that by depositing the epitranscriptomic mark in spliceosome transcripts leads to aberrant splicing, but at the same time creates vulnerability to METTL3 inhibitors.

Automated summary

Mutations in splicing factors are commonly found in CLL, but other mechanisms such as METTL3 overexpression can also lead to abnormal splicing. METTL3 deposits epitranscriptomic marks in spliceosome transcripts, causing aberrant splicing, but also vulnerability to METTL3 inhibitors.