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New research allows scientists to observe abnormal cell mutation in myelodysplastic syndromes disease progression

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Myelodysplastic syndromes (MDS) is a form of blood cancer that is caused by a range of failures of the bone marrow to produce normal functional blood cells. Through reprogramming patient blood cells, researchers recently found a new pathway to study the progression and appropriate treatment of this disease. 

Bone marrow is responsible for manufacturing healthy blood cells, by originally producing stem cells that mature into different types of blood cells. Over time, some of the stem cells acquire random mutations and some of them are damaging and can cause blood diseases such as MDS. 

Although MDS is not a terminal disease, it possibly leads to other blood cancers including leukemia

“Some types of [bad] mutations give advantages to the cell,” Andreea Reilly, a postdoctoral researcher from the team said. “They start taking over. Then you have fewer normal blood cells and more sick ones.” 

To trace the disease’s evolution in cells, the research team pushes blood cells back to a stem cell stage. This process allows only the early disease cells to survive, thus we can capture the cells with the bad mutations that were “the first domino.” 

Currently, with other methods, you can get a snapshot of all the mutations in a patient but you don’t know in what order they occurred or which ones were important in making detrimental changes to the cells and causing the disease.

“We are able to see the history of the disease,” Reilly said. “We can capture and compare the cells [at different stages]. We can run experiments on them.” 

The result helps researchers to understand the various changing disease patterns. Reilly mentioned that having a thorough understanding of cell mutations allows physicians to better predict patients at risk for MDS since mutations can be detected early through screening. 

The challenge in the research is that the cause of MDS is complicated. According to Reilly, there are at least 50 mutations that possibly cause MDS. In this study, the team investigated two different types of mutations and showed that they contributed to two different types of cancers: one that affected the cells’ mitochondria, and the other affected the ability of the cell to repair its DNA. Both types impair cell function and cause disease but in different ways. 

The team is looking at and trying to understand other mutations. 

Every year, more than 10,000 people are diagnosed with MDS in the U.S. According to American Cancer Society, people older than 50 are more likely to get the disease due to natural aging and change in body mechanism. Genetic inheritance of some MDS-related mutations can put people at higher risk for this disease. 

Reilly said studying the pattern of disease-initiating mutations in MDS will allow for a better understanding of the causes of MDS, as well as help with earlier screening and intervention. 

Reach reporter Sunny Wang at science@dailyuw.com. Twitter: @sunnyqwang64

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