PROJECT SUMMARY

As people age, they develop mutations in their blood-forming stem cells – known as clonal hematopoiesis (CH), or pre-leukemia. Although CH can now be detected with high sensitivity, there are no treatments to prevent its progression to myelodysplastic syndrome or a full-blown leukemia. This is because the molecules which are involved in this process are unknown and hence cannot be therapeutically targeted.

Our project aims to identify them by modeling how pre-leukemia arises and takes hold in a bone marrow which is otherwise healthy – the same process as occurs in humans. To achieve this, we are using a special tool called photoactivatable Cre (PAcre), which uses light to precisely induce a genetic change in a single cell which initiates pre-leukemia in a live animal. We will then study growing pre-leukemic cells and their surrounding cells using Image-Seq, a technique we developed that lets us “listen” to their cross-talk.

We hypothesize that through a deeper understanding of the content of this cross-talk, we can identify the molecular “messages” that the surrounding cells send to their pre-leukemic neighbors, thereby promoting their growth and expansion. We believe that in the future, “intercepting” these messages using drugs will prevent the development of myelodysplastic syndrome and leukemia.