AEP was found to break down Elspar, according to JCI paper.


Researchers have identified an enzyme responsible for breaking down and inactivating a childhood leukemia drug. They report that this discovery helps explain why around 20% of patients do not respond to therapy.

Their findings were published in the Journal of Clinical Investigation yesterday in a paper titled “A Dyad of Lymphoblastic Lysosomal Cysteine Proteases Degrades the Key Anti-Leukemic Drug L-Asparaginase.”

The team studied the effect of the drug Elspar (asparaginase) on lymphoblastic leukaemia cells. They found that the enzyme called AEP breaks down the drug and thus stops it from working.

The investigators also discovered that AEP was not found in healthy white blood cells, which are the cells affected by leukemia. They hypothesize that production of AEP and resistance to the drug is the result of a genetic fault in some leukemia cells. 

The researchers think that the presence of AEP could determine whether patients respond to treatment and whether they have an allergic reaction to it. “If our findings in leukemia cells are confirmed in patients, we could be able to test if this drug is the best option before treatment starts,” remarks Vaskar Saha, Cancer Research UK’s pediatric oncologist. “We’re currently recruiting patients from 18 childhood cancer centers in the U.K. to help us discover if this is the case.”


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