“These results really highlight IGF2BP3 as an attractive and valuable therapeutic target,” said lead author Tiffany Tran, a graduate student researcher in UCLA’s molecular, cellular and integrative physiology interdepartmental doctoral program. “By targeting this RNA-binding protein, we would be able to target the cancer cells directly and leave the healthy, non-cancerous cells alone.”

In targeting IGF2BP3, the team also discovered that the protein was not necessary for normal blood development in mice; the blood system appeared mostly intact when the protein was removed. Even mice that were completely deficient of the protein developed normally.

“This was surprising to us because a lot of proteins that are important in cancer are also important in normal tissues,” said Rao, who is also a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

“This is also an attractive target because we have made some real advances in understanding how it works in the cancer cells,” Rao added. “We were able to pinpoint some important RNA molecules that it binds to, which encode other cancer-causing proteins. So if you can remove this protein, you’re able to modify the amount of other cancer-causing proteins.”

While the team studied IGF2BP3 as a target in MLL leukemias, the protein is also highly expressed in about 15% to 20% of other cancer types, including glioblastoma, pancreatic cancer, lung cancer and melanoma.

The next step for researchers is to understand whether the removal of the protein has as strong of an effect against other types of cancer, as well as to develop small-molecule and RNA-based therapeutics to try to interfere with the function of the protein.

Other study authors included Jaspal Bassi, Neha Nibber, Tasha Lin, Jayanth Palanichamy, Amit Jaiswal, May Paing, and Jennifer King, all of UCLA; Julia Philipp, Jolene Draper, Sol Katzman and Jeremy Sanford of UC Santa Cruz; and Oscar Silva of Stanford University.

The work was supported in part by the National Institutes of Health.