"Cell Stem Cell" Small cell populations play an important role in triggering silent cases of hereditary MDS

In the United States, as many as 187,000 people are dealing with myelodysplastic syndrome (MDS), a disease that destroys the bone marrow's ability to produce healthy blood cells

In most cases, MDS is caused by mutations in blood stem cells during a person's lifetime

In 2016, other scientists documented that people with this inherited form of adult MDS have common mutations in the DDX41 gene, but it is not clear what role these mutations play

Their discovery is based on a lot of work to develop a more accurate mouse model of human MDS, which is caused by the DDX41 mutation

The research team concluded that these relatively rare cells in the patient’s bone marrow may indirectly affect the rest of the bone marrow and cause abnormal blood production

Dr.

Although the focus of this study is MDS, similar types of crosstalk between cells with different combinations of mutations may play a role in other diseases

Starczynowski said: "As far as we know, this is the first evidence that inherited or newborn MDS can be mediated by a small number of disease-modifying clones in the bone marrow

What is MDS?

Myelodysplastic syndrome includes a group of diseases that impair bone marrow function

Sometimes MDS is a side effect of cancer radiotherapy or chemotherapy

Patients with advanced MDS require bone marrow transplantation

Detect silent trigger

Starczynowski and his colleagues have been studying MDS for many years

"Cells with this additional DDX41 mutation do not make up most of the bone marrow

Experiments in mice have shown that blood stem cells that have mutations in both copies of the DDX41 gene have defects in their mechanism for making new proteins (called ribosomes)
.
This prevents the proliferation of stem cells and the formation of a normal number of new blood cells
.
Since these cells cannot multiply efficiently, they do not cause bone marrow failure by themselves, but they can affect other cells in the bone marrow, leading to ineffective blood cell production
.

This process may help explain why these patients with MDS can feel completely normal before the onset of the disease suddenly, until later in adulthood
.

Next step

The research team plans to conduct further studies to determine whether targeting cells with slight clonal DDX41 mutations will alter the progression of MDS in the mouse model, and if successful, may lead to potential human drug development
.

This discovery may also serve as a springboard for other studies to find similar crosstalk between potentially overlooked small cell populations and their richer followers
.

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DOI

10.
1016/j.
stem.
2021.
08.
004