New Compound Kills Acute Lymphoblastic Leukemia


Promising study may lead to targeted treatment for patients with ALL.

A new compound has been found that kills acute lymphoblastic leukemia (ALL) involving the gene TAL-1, a recent study suggests.

TAL-1 is a common form of T-cell ALL (T-ALL), which accounts for 15% of all childhood cases of ALL. The new compound, called GSK-J4, was originally created for pharmaceutical research and has never been used as a form of cancer therapy previously.

"It's very exciting because this is the first time anyone has found a potential personalized treatment for this aggressive disease," said senior author Marjorie Brand. "Unlike current therapies, ours targets the offending gene without harming the rest of the body."

Unfortunately, current treatments involve harsh forms of chemotherapy that increase the risk of secondary cancers later in life, as well as stunting the growth of children. Additionally, patients who experience cancer recurrence after treatment are likely to die soon after.

"With the current treatments, you get a 90% cure rate in some of the T-ALL subtypes," said lead author Aissa Benyoucef. "But in the TAL-1 subtype that we're studying, you get only a 50% cure rate. It's very aggressive."

In order to find better treatment options for TAL-1, researchers at the University of Ottawa needed to explore how it worked on a molecular level.

Under certain circumstances, the TAL-1 gene activates certain genes that make white blood cells grow uncontrollably. This allows TAL-1 to transform cells that will eventually become T-cells into cancer cells.

These cancerous cells will eventually spread throughout the body and blood, causing leukemia.

During a study published in Genes & Development, researchers found that in order for TAL-1 to produce cancerous cells, it requires the enzyme UTX.

With the help of the compound GSK-J4, which has the ability to turn off UTX, the growth of the TAL-1 cancer cells were stopped. These findings were tested in mouse models injected with human cells from TAL-1 type leukemia.

The mice were then treated with GSK-J4 over a 3-week period. During this time, researchers found the amount of cancerous cells in bone marrow decreased by 80%. Furthermore, it left the non-cancerous healthy cells unharmed with no short-term effects on other organs within the body.

"While our study is a proof of concept, these promising results might one day lead to a similar targeted treatment for humans," said second author Carmen Palii.

This treatment specifically worked only for TAL-1 subtype, and not any other types of T-ALL. By transplanting cancer cells from human patients into normal mice, the authors showed that the compound can kill leukemia quickly, efficiently, and with no short-term side effects.

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