New drugs effective at killing leukemia cells, early study finds

By Michael Lee

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    TORONTO (CTV Network) — New research has identified a unique form of chemotherapy which preliminary experiments show is effective at targeting different leukemia cells.

Published in the journal Leukemia, a study from researchers at Rice University and the University of Texas MD Anderson Cancer Center has found new potential in various compounds that specifically target mitochondria, which provide energy for cells.

“Although this is very promising, we’re still some distance from having a new treatment we can use in the clinic,” Rice biochemist Natasha Kirienko and corresponding author of the study said in a statement. “We still have a lot to discover.”

The researchers previously screened approximately 45,000 small-molecule compounds to find some that target mitochondria.

For their latest study, they chose eight and found between five and 30 close analogues for each.

The researchers then conducted tens of thousands of tests to determine which were toxic to leukemia cells, either on their own or when combined with existing chemotherapy drugs such as doxorubicin.

The eight compounds were previously shown to target mitochondria by starting a process called mitophagy, or when a cell decommissions and recycles its old mitochondria.

Cancer is known for using mitophagy to fuel itself, the researchers say, with previous research showing leukemia cells have far more damaged mitochondria than healthy ones.

The researchers believed drugs that cause mitophagy could weaken leukemia cells and make them more susceptible to chemotherapy.

In the end, they found six were most effective at killing acute myeloid leukemia cells. Of those, five were also effective at killing acute lymphoblastic leukemia and chronic myelogenous leukemia cells.

All of the mitophagy-inducing drugs caused far less harm to healthy cells, the researchers say.

The experiments also showed several mitophagy-inducing compounds were “significantly” more synergistic with doxorubicin.

For their final experiments, the researchers tested one of the more effective compounds on mice implanted with cancerous cells from a leukemia patient.

The study found the compound was effective at killing acute myeloid leukemia cells in mice.

“We need to refine the dose we think would be best, and perhaps most importantly, we need to test on a wide variety of AML (acute myeloid leukemia) cancers,” Kirienko said.

“AML has a lot of variations, and we need to know which patients are most likely to benefit from this treatment and which are not. Only after we’ve done that work, which may take a few years, would we be able to start testing in humans.”

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Sonja Puzic