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To stop blood cancer, target the bone

Date:
January 19, 2022
Source:
Columbia University Irving Medical Center
Summary:
New research suggests that targeting neighboring bone cells may be a better strategy than targeting malignant stem cells to treat acute myeloid leukemia.
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To stop acute myeloid leukemia, one of the deadliest blood cancers, targeting neighboring bone cells may be a better strategy than directly targeting the cells that give rise to the disease, suggests a new Columbia study.

The new study was published Jan. 19 in Cancer Discovery, a journal of the American Association for Cancer Research.

Acute myeloid leukemia (AML) is one of the hardest-to-treat blood cancers. And though it's possible to achieve remission with drugs that target and destroy the stem cells that give rise to leukemia, the disease usually returns with deadly consequences. Patients relapse when new types of leukemic stem cells that elude all existing treatments surface.

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

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

That's because the osteoblasts are lured into helping leukemia stem cells, Kousteni's team, led by Marta Galán-Díez, PhD, found. The new study reveals how leukemia cells lure the osteoblasts to function to their advantage by releasing a molecule called kynurenine. Kynurenine binds to a serotonin receptor (HTR1B) on the osteoblasts, sending the message to osteoblasts to help nurture leukemic cells by secreting an acute phase response protein (SAA1). SAA1 then tells the leukemia cells to make more kynurenine, and a vicious cycle ensues that leads to more disease progression.

The crosstalk between leukemia cells and osteoblasts can be broken, Galán-Díez and Kousteni found, suggesting a way forward for new AML treatments. In experiments with mice, they found that genetically eliminating the serotonin receptor that binds kynurenine blocks the progression of leukemic cells.

And in humanized mice carrying leukemia cells from patients and experiencing an AML relapse, an experimental drug that inhibits kynurenine synthesis "had a substantial effect in combination with traditional chemotherapy, slowing disease progression," Galán-Díez says. (The drug, called epacadostat, is being tested in other cancers).

In the same study, Kousteni and Galán-Díez observed increasing levels of kynurenine and SAA1 in AML patients and in patients with myelodysplastic syndrome (MDS), another hematological cancer that often transforms to AML. Levels of both molecules increase with MDS progression to AML and SAA1 promotes proliferation of MDS and AML cells from patients, suggesting the same partnership between MDS or leukemia cells and osteoblasts is active in the human form of disease.

"The advantage of this approach is that it doesn't matter which stem cells are causing the disease. They all 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 says.

In addition, the same approach may also prevent pre-leukemic conditions like MDS from progressing.


Story Source:

Materials provided by Columbia University Irving Medical Center. Note: Content may be edited for style and length.


Journal Reference:

  1. Marta Galan-Diez, Florence Borot, Abdullah Mahmood Ali, Junfei Zhao, Eva Gil-Iturbe, Xiaochuan Shan, Na Luo, Yongfeng Liu, Xi-Ping Huang, Brygida Bisikirska, Rossella Labella, Irwin Kurland, Bryan L Roth, Matthias Quick, Siddhartha Mukherjee, Raul Rabadan, Martin Carroll, Azra Raza, Stavroula Kousteni. Subversion of serotonin-receptor signaling in osteoblasts by kynurenine drives Acute Myeloid Leukemia. Cancer Discovery, 2022; candisc.0692.2021 DOI: 10.1158/2159-8290.CD-21-0692

Cite This Page:

Columbia University Irving Medical Center. "To stop blood cancer, target the bone." ScienceDaily. ScienceDaily, 19 January 2022. <www.sciencedaily.com/releases/2022/01/220119121335.htm>.
Columbia University Irving Medical Center. (2022, January 19). To stop blood cancer, target the bone. ScienceDaily. Retrieved December 4, 2024 from www.sciencedaily.com/releases/2022/01/220119121335.htm
Columbia University Irving Medical Center. "To stop blood cancer, target the bone." ScienceDaily. www.sciencedaily.com/releases/2022/01/220119121335.htm (accessed December 4, 2024).

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