'Jumping' genes can prevent blood cancers: Study

Transposons are DNA sequences that can move, or jump, from one location in the genome to another when activated. These "jumping" genes are a source of genetic mutations responsible for a number of human diseases.

The findings, published in the journal Nature Genetics, can help predict how patients will respond to cancer therapies and find new therapeutic targets for acute myeloid leukemia (AML) -- the deadliest type of blood cancer in adults and children.

In the study, a team of scientists at the Children's Medical Center Research Institute (CRI) at University of Texas Southwestern focussed on a type of transposons known as long interspersed element-1 (L1) retrotransposons.

They found that activating L1 can lead to genome instability and, in turn, it can activate a DNA damage response that triggers cell death or eliminates the cell's ability to replicate itself.

When researchers screened human AML cells to identify genes essential for cancer cell survival, they found MPP8 -- a known regulator of L1 -- to be selectively required by AML cells.

Analysing human and mouse leukemia cells, they found that MPP8 blocked the copying of L1 sequences in the cells that initiate AML and when the activity of L1 was turned on, it could impair the growth or survival of AML cells.

MPP8 thus suppressed L1 in order to safeguard the cancer cell genome and allow AML-initiating cells to survive and proliferate.

"Our initial finding was a surprise because it's been long thought that activated transposons promote cancer development by generating genetic mutations. We found it was the opposite for blood cancers, and that decreased L1 activity was associated with worse clinical outcomes and therapy resistance in patients," said Jian Xu, Associate Professor in the CRI.