BU researchers: Key enzyme in a pathway of T-cell leukemia offers a new target

Boston U.'s Hui Feng

A blood cancer that is fatal in 20% of children and 50% of adults has an Achilles' heel that could be exploited by drug developers.

Researchers headed up by Dr. Hui Feng at the Boston University Medical Center concluded that T-cell leukemia cells rely on certain metabolic pathways for their growth and survival, and they point toward a key enzyme in this process that may offer a solid target for new research.

The group published their work online this month in the journal Leukemia.

At present, the majority of treatments for T-cell leukemia are highly toxic to the patient, which is driving new work like this to find better drugs for this type of cancer.

The Boston team used an experimental mouse model of T-cell acute lymphoblastic leukemia and screened for genes that changed in these cells. From this they identified a gene that codes for an enzyme--called DLST--which is important in the TCA or Kreb cycle used by an organism for producing energy.

"Researchers have wrongly assumed that cancer cells do not use the TCA cycle to support their growth. Our new findings provide solid evidence that these cancer cells depend on the TCA cycle for their survival," said Feng.

They pursued the DLST enzyme as a potential culprit in the progression of the cancer. By inhibiting the enzyme in human T-cell leukemia cells they found that they could effectively kill the cancer cells.

"Additionally we demonstrated the importance of DLST in T-cell leukemia development, and have identified a targetable enzyme for T-cell leukemia treatment," Feng added.

If DLST inhibition works in other types of aggressive cancers, the Boston team believes the finding will extend to other cancer cells and may provide a new treatment angle.

- here's the release
- get the journal abstract

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