Research breakthrough identifies how mutated genes reprogram blood stem cells in leukemia

Mutated genes in leukemia can reprogram blood stem cells, affecting blood cell production.
Mutated genes in leukemia can reprogram blood stem cells, affecting blood cell production.

Researchers have made a breakthrough in understanding how mutated genes in leukemia reprogram blood stem cells and send them spiraling out of control. The findings help to explain the early development of leukemia, representing the essential first step to developing new treatments for patients based on these findings.

The role of one specific mutation in the FLT3 gene found in acute myeloid leukemia (AML) was investigated in the study by Professors Peter Cockerill, PhD, and Constanze Bonifer, PhD, both of the University of Birmingham, United Kingdom, which was published in Cell Reports (2015; doi:10.1016/j.celrep.2015.06.069).

Younger patients with AML have a better prognosis, but overall survival rates are very poor and new treatments are needed.

FLT3 is a protein that normally makes sure that blood stem cells produce just the right number of blood cells every day. When mutated, it sends the wrong signals and keeps the stem cells expanding out of control, swamping the body with abnormal blood cells.

"We found that the mutated FLT3 protein always sends the same signals to the same set of genes in all AML patients that have this mutation. By finding out which signals and genes are the targets, we now have new targets that will allow us to attack this pathway," said Cockerill.

The team found that the mutated FLT3 protein used one specific signaling pathway inside the cell to activate more than 1,000 different targets within the DNA, leading to the abnormal activation of more than 100 genes in patients with the mutation. Many of these genes were already known to contribute to cancer by sending growth signals.

The project was funded by Leukaemia and Lymphoma Research, a cancer charity in the United Kingdom. Matt Kaiser, MD, head of research at Leukaemia & Lymphoma Research, said: "Unfortunately there have been no significant improvements in survival rates for acute myeloid leukemia in the last two decades. These findings provide renewed hope for developing new treatments for this aggressive type of leukemia."

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