Christian Hurtz, PhD

Temple University

Titles + affiliations

Assistant Professor, Department of Medicine
Temple University

Research

DYRK1A Inhibition Results in the Activation of the Proapoptotic Molecule BIM and Consequently Sensitizes KMT2A-R ALL cells to BCL2 Inhibition

Summary

KMT2A-rearranged acute lymphoblastic leukemia (KMT2A-R ALL) is the most common ALL subtype in infant ALL and also common in older children with ALL. KMT2A-R ALL is a deadly disease that does not respond well to chemotherapy treatments and often returns after being treated. Our goal is to identify molecules that are important for the health of KMT2A-R leukemia cells, which we can attack with specific medicines called inhibitors. We identified in our studies that KMT2A-R leukemia cells need the signaling molecule DYRK1A to multiply and grow, a process called cell proliferation. DYRK1A regulates proliferation by transmitting information to other signaling molecules, which regulate cell proliferation and cell health. Using a specific inhibitor that prevents DYRK1A from transmitting signals did not kill the leukemia cells because, as a protective mechanism, some molecules are able to inactivate cell death. Our study showed that one molecule in particular is important for protecting leukemia cells against DYRK1A inhibition. This molecule is called BCL2. We are now testing in mouse models that were generated from infant KMT2A-R leukemia cells whether using a two-medicine treatment approach to inhibit DYRK1A and BCL2 can kill KMT2A-R leukemia cells. If this two-medicine treatment approach proves to be better than the currently available chemotherapy treatments, we aim to test this new strategy in new pediatric clinical trials.

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Leukemia Research Foundation grant
$100K awarded in 2022

Disease focus
Acute lymphoblastic leukemia (ALL)

Research focus
Treatment (targeted therapy)