Eliminating RNA-binding protein improves survival in aggressive leukemia

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"... The research ... could aid in the development of targeted therapies for cancers that have high levels of the RNA-binding protein IGF2BP3 — especially acute lymphoblastic and myeloid leukemias that are characterized by chromosomal rearrangements in the mixed lineage leukemia (MLL) gene.

In these MLL-rearranged leukemias, IGF2BP3 attaches to certain RNA molecules that carry genetic instructions for cancer-related proteins, markedly amplifying cancer development. ...

team used the powerful gene-editing tool known as CRISPR-Cas9 to remove IGF2BP3 from both MLL-leukemic mice and cell lines. The effects on survival, they found, were striking.

Of the leukemic mice that had IGF2BP3 deleted, approximately 75% had an increase in overall survival, and 50% were leukemia-free. ..."

"... Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. ..."

Eliminating RNA-binding protein improves survival in aggressive leukemia | UCLA: A team led by UCLA scientists found that removing IGF2BP3 selectively targets cancer cells while leaving healthy cells alone.

The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis (open access)