New study suggests targeting osteoblasts to stem cells

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New study suggests targeting osteoblasts to stem cells

Washington ANI - January 23, ANI To stop acute myeloid leukaemia, one of the deadliest blood cancers, targeting neighbouring bone cells can be a better strategy, according to a recent study.

Acute myeloid leukaemia AML is one of the hardest to treat blood cancers. It's possible to achieve remission with drugs that target and destroy the stem cells that give rise to leukaemia, but the disease usually returns with deadly consequences. When new types of leukemic stem cells are eluded by all existing treatments, patients relapse.

Cancer researcher Stavroula Kousteni, PhD, said that it is challenging to develop additional drugs that target new stem cells because cancer will eventually mutate to circumvent the drugs.

Her new study shows that targeting neighbouring cells in bone marrow osteoblasts, the cells that make bone - could turn a friendly environment for leukaemia cells into a hostile environment.

The osteoblasts are lured into helping leukaemia stem cells, Kousteni's team, led by Marta Galan-Diez, PhD, found. The new study showed how leukaemia cells lure osteoblasts to their advantage by releasing a molecule called kynurenine.

On the osteoblasts, kynurenine binds to a serotonin receptor HTR 1 B to send the message to osteoblasts to help nurture leukemic cells by secreting an acute phase response protein SAA 1 SAA 1 and telling the leukemia cells to make more kynurenine, and a vicious cycle leads to more disease progression.

Galan-Diez and Kousteni found a way forward for new AML treatments, which can be broken by the crosstalk between leukaemia cells and osteoblasts. In experiments with mice, they found that genetically eliminating the serotonin receptor that binds to kynurenine blocks the progression of leukemic cells.

An experimental drug that inhibits kynurenine synthesis had a significant effect in combination with traditional chemotherapy, slowing disease progression, according to Galan-Diez, in humanized mice carrying leukaemia cells from patients and experiencing an AML relapse. The drug, called epacadostat, is being tested in other cancers. In the same study, Kousteni and Galan-Diez observed increasing levels of kynurenine and SAA 1 in AML patients and in patients with myelodysplastic syndrome MDS, another haematological cancer that often transforms to AML.

Both molecules increase with MDS progression to AML and SAA 1 promotes the proliferation of MDS and AML cells from patients, suggesting that a partnership between MDS or leukemia cells and osteoblasts is active in the human form of the disease.

The advantage of this approach is that it doesn't matter which stem cells are causing the disease. They need osteoblasts to grow, and if we can stop these two types of cells from communicating, we might be able to stop the disease, Kousteni said.