Let me tell you, folks, we’ve got some incredible discoveries in the world of leukemia, specifically in the tough battle against KMT2A::AFF1 rearranged leukemia. This is a big deal, a very aggressive form of leukemia in kids, and we’re talking about something that could change the game – circular RNAs, or circRNAs. They’re not just any molecules; they’re powerful players that could be the key to new treatments.

We’ve looked into these circRNAs, and what we’ve found is huge. These little guys are dysregulated in leukemia cells – that means they’re not behaving like they should. And we’re not talking about just a few; there’s a whole landscape of them. Sure, we knew about some bad actors like circHIPK3 and circZNF609, but there are many more we’re just starting to understand.

Now, we did some serious work, a loss-of-function screening, and we’ve identified some real troublemakers: circFKBP5, circKLHL2, circNR3C1, and circPAN3. When we silence these guys, leukemia cells stop proliferating like crazy and start dying like they’re supposed to. And when we looked at more patients, the evidence was clear: these oncogenic circRNAs are not just up to no good, they’re part of a bigger network causing trouble.

And get this – there’s one, circAFF1, that’s really making waves in a subset of cases. It’s like the boss of the bad guys.

So, what we’ve got here is a major breakthrough. These circRNAs, they’re not just bystanders; they’re active players keeping the cancer cells alive and kicking. But now that we know who they are, we can target them, and that’s going to be fantastic for treating this tough leukemia. We’re talking about a whole new strategy to knock down this disease and make a huge difference for these kids. Believe me, it’s going to be great.