Attending Physician, The Children’s Hospital of Philadelphia

Assistant Professor, The University of Pennsylvania

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Thankfully, most children with ALL are cured with a combination of chemotherapy and immunotherapy. However, ALL is so common that relapsed ALL is still a major cause of overall childhood mortality. Most of the time the reason why a child relapses is not known.

Acute lymphoblastic leukemia (ALL) is different from acute myeloid leukemia (AML). AML needs very different chemotherapy. Also, ALL immunotherapy does not work against AML cells. We recently discovered that some patient’s ALL contains small populations of leukemic cells that look more like AML. This raises the possibility that patients who have such populations are more likely to relapse when treated like ALL. It is possible that this type of leukemia could need different therapy. This could mean different chemotherapy, or novel immunotherapy that is tailored to the surface marker on these cells. We conducted single cell profiling of these rare populations in patient cells, and found surface markers that distinguish these leukemic cells from normal bone marrow. In this proposal, we will (1) determine more precisely how many and which patients have these AML-like subpopulations, and (2) develop a CAR-T cell based strategy to target these cells.