Reddits lucky to have someone like you summarize this stuff!

You’d get a kick out of KMT2a. The protein is..3700? residues, has a heap of domains, and gets cleaved into two, something like a 320kD and 180kD. The pull-down assays bring down a ton of things where many of the proteins correspond to mutations seen in cancer. Crystal structure was apparently a challenge.



30% for AML seems good.

If you look at the metric of pathologist workflow and number of times we have to present at tumor boards…KMT2a leukemias are often a lotta work. Induction chemo often doesn’t work well. They recur all the time. They can be 20-30% of pediatric ALL that doesn’t respond to CAR-T (cell based therapy seen in the news for dramatic effect and obscene cost). If you could precondition patients with this type of leukemia before CAR-T more might be eligible.

Many of the patients aren’t healthy enough for a haircut either, so any treatment that doesn’t often kill em in the process (marrow transplant) is especially good.



Pedantic: KMT2A-R (lysine’s amino acid abbreviation is K, MethylTransferase 2A - Rearranged). For the hematologists and oncologists from a while ago, KMT2a used to be called MLL. Nasty disease.

KMT2a is about 4-5% of acute myeloid leukemia in adults, maybe 20% in kids (but kid AML is rare, their leukemia is mostly ALL, although KMT2a can also be rearranged in ALL, because MLL stood for “mixed lineage leukemia” cause it couldn’t seem to make up its mind which type it was). Sorta don’t think it shakes out to an actual 10%, but if you look at the cases where people do badly it’s enriched.

NPM1 is a common form of AML, 30% seems about right…just for AML. But when you factor in CLL, CML, and other forms of leukemia, it’s not 30% of all leukemias.

TL;DR: this works in a disease where not much works. Percentages are hard when the denominator isn’t made clear, and this is especially true here because there are a lot of leukemia subtypes.