An enzyme that is responsible for the breakdown of specific amino acids in food plays a key role in the development of leukemias and brain cancer. The researchers have discovered a surprising link between energy metabolism and the epigenetic code. These labels in the DNA of cancer stem cells determine the activity of genes and many cellular functions.
Acute myeloid leukemia AML is an aggressive type of blood cancer that often relapses in the wake of successful initial treatment. Stem cells that are resistant to therapy are believed to be responsible. Reseachers examined patient samples by comparing the composition of proteins of AML stem cells and leukemia cells without stem cells properties.
The investigators found suspiciously high levels of an enzyme called BCAT1 in the stem cells. These levels rose even higher during a cancer recurrence. The researchers considered this to be a clue that BCAT1 might be linked to therapy resistance. Cancer researchers have suspected for some time that the BCAT1 enzyme, which is responsible for the breakdown of specific proteins in food, plays a role in the development of malignant tumors.
They discovered that an overproduction of BCAT1 increases the aggressiveness of malignant brain tumors and breast cancer. BCAT1 reduces the levels of this key molecule and this leads to increased levels of chemical labels in the DNA. The tiny methyl groups that are attached to DNA determine whether particular genes are active or silent and, thus, have an immense impact on all cellular functions.
They increase cancer-promoting methylation of DNA. AML is known for an extremely heterogeneous pattern of genetic alterations. However, misregulated methylation with its drastic consequences for the whole cell appears to be a common characteristic of this malignant disease.
The finding that BCAT1 drives cancer-promoting methylation in AML stem cells and other cancer stem cells opens up new options for therapy. A blockade of the enzyme using a targeted agent might normalize DNA methylation and thereby reduce cancer spread and therapy resistance.
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