GATA3

And so they show that around these points, potential points of entry, there's accumulation of CD4 cells that they show can be derived from something that happens in the gut.

So what do they show, basically? They have different mouse models in which they initiate either responses that are Th17, um, uh, uh, biased, for example, against, uh, Citrobacter rodentium or, uh, DSS colitis, or things that are, um, Th2, um, biased with a, a expression of GATA3 or with a schistosoma, um, m- mouse model, uh, or a different one wi- in which they induce Th1 responses.

And they find that although the-- they couldn't find differences in the, in the, in the spleenid- in the spleen very much, they could identify CD4 T cells of kind of similar characteristics in the dura of the mice.

And then, um, they show by, um, looking into, for example, paired, uh, TCR sequencing, uh, in the dura, in the duodenum or like kind of in the gut, uh, that there's a lot of shared, uh, uh, clonotypes between the, the gut and the dura.

We continue to chip away at these cases for the unstudied cases, and I'll just show one example from our group in a Japanese study that were published at the same time recently in Blood, where another group of cases with deregulation of another gene called FOXF1 very lineage-ambiguous leukaemias that have often three different lineage sets of markers in the same cases, again driven by an enhancer rearrangement mechanism activating this gene FOXF1.

These cases are often GATA3 mutant, which is often a harbinger from focus testing that this is the type of leukaemia present, and these cases have their own vulnerability also to venetoclax but also to other agents here, ruxolitinib and a less widely studied agent called a PIM inhibitor.

So again, another subtype of leukemia.

There are robust ways to identify the cases and also potential therapeutic approaches.

And basically there's a transcription factor that gets bound to the promoter of the HP1.

And this is different to, this is not dependent on, for example, GATA3, which is the structural factor that really characterizes LC2s, but it's a separate wiring, genetic wiring that is guiding this upregulation.

And So when they test in disease models where they have challenges that generate airway inflammation, they show that the serotonin in the bronchoalveolar lavage does increase in context of inflammation and inflammation.

Asthma models, IL-33 challenge.

Where we actually do much better is metastasis.

Because in metastasis, lineage markers like cytokeratins, CTF1, GATA3, melanoma markers, they actually let a pathologist pick out even single viable tumor cells in a sea of necrosis.

In glioma, we lean on mutation-specific antibodies where we have them, like the IDH1, R132H mutation, the H3K27M.

So for these, we have mutation-specific antibodies.