Leukemia Cells Activate Cellular Recycling Program
Published:02 Jan.2024 Source:Goethe University Frankfurt
In a recent study, scientists led by Professor Stefan Müller from Goethe University's Institute of Biochemistry II investigated a specific form of blood cancer known as acute myeloid leukemia, or AML. In about a third of AML patients, the cancer cells' genetic material has a characteristic mutation that affects the so-called NPM1 gene, which contains the building instructions for a protein of the same name.
The mutated NPM1 variant (abbreviated as NPM1c) is an important factor in the development of leukemia. The altered protein intervenes in autophagy, an important cell process that consists of a metabolic pathway through which the cell recycles its own structures. NPM1c promotes the production of both autophagosomes as well as lysosomes. It binds to a central regulator of the autophagosome-lysosome system called GABARAP, and thereby activates it.
Using computer simulations, researchers have shown that this binding of NPM1c and GABARAP has an atypical structure. Experimental structural biology data confirm the simulation's results, based on which it may now be possible to develop active substances that specifically influence the binding of NPM1c to GABARAP and thus combat the growth of leukemia cells.