Role of Stem Cell Niche in Leukemia Development and Treatment

Stem cells in the bone marrow are known to play an important role in the development of leukemia

The environment of bone marrow stem cells plays a key role in the development and treatment of leukemia. This has emerged from research by internist-haematologist Prof. Marc Raaijmakers. His research group was the first to map the interaction between stem cells and their environment in patients with acute myeloid leukemia.

‘The stem cells in the bone marrow do not live in a vacuum’, Raaijmakers begins. ‘They are surrounded by specialized cells that help them survive and function. These cells together form the stem cell niche. Our research shows that inflammation in this stem cell niche can drive the development of leukemia. But at the same time they increase the effectiveness of chemotherapy.’

Derailed stem cells
Stem cells in the bone marrow are known to play an important role in the development of leukemia. Normally these stem cells grow into blood cells, but this goes wrong in acute leukemia. A mutation causes the stem cells to change into tumor cells. ‘We suspected that the cells surrounding the stem cells play an important role in the formation of tumours. Thanks to new techniques, we can now finally investigate these stem cell niches properly,’ says Raaijmakers. The results of his research were recently published in the journal Blood Cancer Discovery.

Inflammation
The researchers, led by postdoc Lanpeng Chen, compared bone marrow from healthy individuals with bone marrow from patients with acute myeloid leukemia (AML). In patients with AML, cells in the stem cell niches showed signs of inflammation, says Raaijmakers. ‘The inflammation in stem cell niches inhibits the development of healthy stem cells. The tumor cells, on the other hand, do not suffer from the inflammation and were able to quickly take over from the healthy stem cells.’

chemotherapy
Thus, tumor cells appear to benefit from inflammation in the stem cell niche. Despite this, patients with high levels of inflammation had a better survival rate after chemotherapy. Raaijmakers thinks this is because inflamed niches make tumor cells vulnerable to chemotherapy. ‘Tumor stem cells use the niche cells during chemotherapy to survive. But an inflamed niche offers insufficient protection. As a result, the tumor cells in an inflamed niche are more susceptible to chemotherapy.’

Treatments
Raaijmakers sees two ways in which his findings can contribute to the treatment of leukemia. ‘In the first instance you would like to inhibit the inflammation in the stem cell niches in order to slow down or prevent the formation of tumor cells and the development of AML. If the disease has developed and you start chemotherapy, you want to stimulate the inflammation so that the tumor cells do not benefit from the niche cells.’

However, the road to the clinic is still long, according to the internist-haematologist. ‘The next step is to further test these concepts in animal models and to study exactly which inflammatory signals are important. Only then will we know whether there are new targets for a treatment.’

HOVON studies
In this study, basic and clinical research came together: the latest research techniques were applied to clinically obtained bone marrow tissue. This bone marrow tissue comes from the biobank of the drug studies of HOVON foundation. This foundation is housed in the Erasmus MC and facilitates drug research into hematological disorders.

Bron: Erasmus MC

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2023-08-02 08:00:35
#Bone #marrow #stem #cells #influence #development #leukemia