iwAL 2026 | Insights into the potential of therapeutically targeting leukemic stem cell properties in AML
Stephen Nimer, MD, Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, shares insight into the properties of leukemic stem cells that can be therapeutically targeted, including self-renewal and survival signals. Dr Nimer emphasizes the importance of understanding the fundamental properties of all acute myeloid leukemia (AML), regardless of the specific mutations present, in order to develop effective therapies. This interview took place at the 8th International Workshop on Acute Leukemias (iwAL 2026), held in Boston, MA.
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Transcript
We need to understand what are the properties of normal hematopoietic stem cells that the leukemic stem cell has. The leukemic stem cell has the ability to sustain itself, and that involves self-renewal first and foremost. It involves survival signals. And the question is, can that be therapeutically exploited? Does normal hematopoiesis use slightly different signals for self-renewal? The other component is the block and differentiation...
We need to understand what are the properties of normal hematopoietic stem cells that the leukemic stem cell has. The leukemic stem cell has the ability to sustain itself, and that involves self-renewal first and foremost. It involves survival signals. And the question is, can that be therapeutically exploited? Does normal hematopoiesis use slightly different signals for self-renewal? The other component is the block and differentiation. And what we’ve been focused on is, can you work on these properties independent of the mutation? So these are fundamental properties of all AML. And each mutation that coexists in AML contributes to some component. There are kinase mutations, RAS mutations that drive proliferation. There can be upregulation of anti-apoptotic proteins. But fundamentally, we’ve been focused a lot on self-renewal. Each stem cell, when it divides, can either become two stem cells, one stem cell and one daughter cell, or two daughter cells. And if you started with a leukemic stem cell and you generated two daughters, now you don’t have any leukemic stem cells anymore from that one cell. And that would be a very effective way of treating leukemia. Today we heard a little bit about differentiation therapies, and they probably work in part by taking a leukemic stem cell and causing it to differentiate so it no longer has stem cell properties.
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