iwAL 2026 | Targeting RUNX1 in AML: a leukemia stem-cell dependency
Stephen Nimer, MD, Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, discusses the potential of therapeutically targeting RUNX1, a leukemia stem cell dependency, identified through induced pluripotent stem cell (iPSC) models of human acute myeloid leukemia (AML). Dr Nimer explains that because transcription factors are difficult to target directly, researchers are investigating inhibition of the enzymes that activate RUNX1, and notes that further research is needed to test whether drugs that mimic this inhibition are effective in AML. This interview took place at the 8th International Workshop on Acute Leukemias (iwAL 2026), held in Boston, MA.
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Transcript
So there’s two components. And I’d say that the iPS work is done, generally we’ve done it with Eirini Papapetrou at Mount Sinai. And so that’s using human cells to model AML. And there’s been a lot of advances in terms of generating iPS cells from AML, from human AML, and then converting it back to the human AML cells and grafting it in immunodeficient mice and studying that...
So there’s two components. And I’d say that the iPS work is done, generally we’ve done it with Eirini Papapetrou at Mount Sinai. And so that’s using human cells to model AML. And there’s been a lot of advances in terms of generating iPS cells from AML, from human AML, and then converting it back to the human AML cells and grafting it in immunodeficient mice and studying that. And that work identifies RUNX as being very important. There’s also a lot of mouse work where generating a leukemia in the mouse, probably the same as in humans, requires some ability to differentiate. And so RUNX is involved in differentiation, and therefore it’s often essential in the mouse models as well. And so then the question is, how do you target a transcription factor? And in general, people say the transcription factor binds DNA so tightly that you can’t really impact that. So what we’ve been studying is how RUNX1 function gets activated by different enzymes, by acetyltransferases, methyltransferases, kinases, that if you can inhibit those enzymes, you can prevent RUNX1 from being properly activated. And that is another way of eliminating its function. And if you eliminate its function, you can treat leukemia. We know there’s a germline mutation in RUNX1 in people with FPD/AML, familial platelet disorder with a predisposition to leukemia. And so people have been studying cells from those individuals who are born with a RUNX1 mutation. And the answer is, how can you keep their stem cells healthy? How do you prevent them from getting a second mutation? And so the hope is that drug companies are developing inhibitors of these enzymes. One good example is p300. So it’s sometimes referred to as p300/CBP, which are two distinct but family relatives of lysine acetyltransferases. And there’s now two drugs that are in patients that are p300-CBP inhibitors. They’re being used in myeloid diseases, in multiple myeloma, in prostate cancer. And there’s already starting to see some activity there. And so hopefully it’ll continue with pharma developing these sort of inhibitors that we can then test in AML.
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