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Their study focuses on a type of acute lymphoblastic leukemia (ALL) that involves a gene called TAL-1. Dr. Marjorie Brand and her team discovered that GSK-J4 can kill this form of cancer. By transplanting cancer cells from human patients into normal mice, the authors showed that the compound can kill the leukemia quickly, efficiently, and with no short-term side effects. GSK-J4 was created by the pharmaceutical industry for research purposes, and has never been used as a cancer therapy.
“It’s very exciting because this is the first time anyone has found a potential personalized treatment for this aggressive disease,” said Dr. Brand, a senior scientist at The Ottawa Hospital and professor at the University of Ottawa. “Unlike current therapies, ours targets the offending gene without harming the rest of the body.”
Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. T-ALL affects T-cells and represents 15% of childhood ALL cases. This study in particular dealt with a common form of T-ALL called TAL-1.
Today the treatment is the same for all forms of T-ALL: harsh chemotherapy with side-effects including risk of secondary cancers later in life and stunted growth in children. If the cancer returns, patients usually die soon after. “With the current treatments, you get a 90% cure rate in some of the T-ALL subtypes,” said lead author Dr. Aissa Benyoucef. “But in the TAL-1 subtype that we’re studying, you get only a 50% cure rate. It’s very aggressive.”
The team looked at the TAL-1 gene, which in certain circumstances can transform the cells that will become T-cells into cancer cells. TAL-1 does this by activating genes that make white blood cells grow uncontrollably. TAL-1 has a weak spot: It needs enzyme UTX, to trigger cancer production. So when Dr. Brand’s team used GSK-J4 to turn off UTX, it completely stopped the growth of TAL-1 type cancer cells. This treatment specifically worked only for TAL-1 subtype, and not any other types of T-ALL.
The team tested these findings in mouse models injected with cells from human TAL-1 type leukemia. After treating for over 3 weeks, they found the number of cancer cells in their bone marrow decreased by 80% with no short-term effects on other cells and organs of the body. The team is now conducting pre-clinical studies in mouse models, looking at the effects of increased doses and long-term side effects of GSK-J4.
http://www.ohri.ca/newsroom/newsstory.asp?ID=743
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