The role of mast cells in the development of chronic myeloid leukaemia (CML) has been revealed for the first time, German researchers have reported.
Scientists at the University of Freiburg, Germany, say their findings could help to develop new therapies for this type of leukaemia.
Mast cells of the immune system play a decisive role in the defence against pathogens, but also in allergies. They release proinflammatory cytokines, which are crucial for the immune response. However, these cytokines are also frequently found in the microenvironment of tumours and are believed to promote cancer development.
Now a research team, led by Dr Sebastian Halbach, Melanie Langhammer and Dr Julia Schöpf, has confirmed for the first time that mast cells play a crucial role in the development of CML.
Using a mouse model for CML, the team showed that the BCR-ABL oncogene, which causes CML, also leads to an increased number of mast cells in the bone marrow.
Writing in the latest edition of the journal Leukemia, they also found the BCR-ABL gene led to a significantly increased release of proinflammatory cytokines.
However, mice that lacked mast cells did not show an increase in proinflammatory cytokines and did not develop splenomegaly, which is frequently observed in leukaemias.
The findings from the animal model were supported by additional research using clinical data and samples from CML patients. The team showed that patients with severe splenomegaly often have an increased number of mast cells in their bone marrow. In addition, patients with increased concentrations of tryptase, an enzyme released by mast cells, also had increased levels of proinflammatory cytokines in their blood.
Dr Halbach said: “These results could be the basis for new therapeutic approaches.”
The discovery of the BCR-ABL oncogene as the trigger for CML led to the development of tyrosine kinase inhibitors (TKIs), which revolutionised treatments of the disease. But even with these drugs, it is not often possible to eliminate all malignant cells, especially the leukaemia stem cells in the bone marrow. Resistances to the TKIs can develop during therapy, leading to relapse, while lifelong use of TKIs is associated with a high burden of side effects for patients.
Dr Halbach says for these reasons it is important to develop new and more effective therapies. He added the study also offers suggestions for further research into other types of cancer.
“I am convinced that mast cells also play an important role in other cancers, since proinflammatory cytokines are often found upregulated here as well,” he said.
Source:
Langhammer M, Schöpf J, Jaquet T, Horn K, Angel M, Spohr C, Christen D, Uhl FM, Maié T, Jacobi H, Feyerabend TB, Huber J, Panning M, Sitaru C, Costa I, Zeiser R, Aumann K, Becker H, Braunschweig T, Koschmieder S, Shoumariyeh K, Huber M, Schemionek-Reinders M, Brummer T, Halbach S. (2023) “Mast cell deficiency prevents BCR::ABL1 induced splenomegaly and cytokine elevation in a CML mouse model.” Leukemia, doi: 10.1038/s41375-023-01916-x
Link: https://www.nature.com/articles/s41375-023-01916-x
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