Myelodysplastic Syndromes May Start In Bone Marrow Stem Cells (ASH 2011)
New research supports the theory that myelodysplastic syndromes has its origins in bone marrow stem cells.
“We have experimentally demonstrated for the first time that [myelodysplastic syndromes] stem cells can transplant and initiate disease. That means that in order to cure the disease, we must target and eradicate this cell population,” said Dr. Christopher Park, the lead researcher on the study from Memorial Sloan-Kettering Cancer Center in New York.
Dr. Park explained that the findings will probably not have immediate implications for myelodysplastic syndromes (MDS) patients. However, he pointed out that his study demonstrates that stem cells from MDS patients need to be studied more carefully.
Dr. Park presented the findings at the 2011 meeting of the American Society of Hematology (ASH) in December.
Bone marrow stem cells, known scientifically as hematopoietic stem cells, are found in the bone marrow. They have the potential to mature into any type of blood cell, such as red blood cells, white blood cells, or platelets.
MDS patients do not produce healthy, mature blood cells.
Researchers have hypothesized that this blood cell production defect may be related to unhealthy bone marrow stem cells giving rise to unhealthy blood cells.
Previous studies have shown that MDS patients with chromosomal abnormalities in their blood cells also have high levels of bone marrow stem cells with chromosomal abnormalities. These findings suggest that MDS may start in bone marrow stem cells.
However, according to the authors of the current study, the prior studies did not examine MDS cases harboring a wider range of chromosomal abnormalities or determine whether the abnormal bone marrow stem cells actually had the ability to initiate MDS.
In this study, bone marrow stem cells were purified from the bone marrow of MDS patients and from healthy people who were the same age as the patients.
The researchers found MDS patients and healthy people of the same age had similar numbers of bone marrow stem cells. Similarly, there was no difference in the number of bone marrow stem cells that were dying.
However, when the researchers examined bone marrow stem cells that matured into myeloid progenitor cells (a more mature type of bone marrow stem cell that only develops into white blood cells), they found that the myeloid progenitor cells from MDS patients had a higher rate of cell death than those from the healthy people (39 percent versus 18 percent, respectively).
The researchers then compared the purified bone marrow stem cells from ten low-risk MDS patients with those from ten healthy adults.
The researchers determined which genes were actively involved in protein production and how active they were. They found that many genes in bone marrow stem cells from low-risk MDS patients had altered levels of protein production compared to those from healthy adults, including genes that regulate cell growth and proliferation as well as genes that are responsible for inflammatory response.
The bone marrow stem cells from the low-risk patients were then analyzed for chromosomal abnormalities.
In bone marrow stem cells from the five patients with known chromosomal abnormalities, 84 percent to 92 percent of the bone marrow stem cells had the chromosomal abnormalities. However, a small number of healthy bone marrow stem cells appeared to coexist with the abnormal ones, suggesting that the abnormal cells did not completely replace the healthy cells.
The researchers then transplanted purified bone marrow stem cells from MDS patients into mice. They were able to show that the transplanted abnormal stem cells grew in the mice and that they showed similar defects in making mature blood cells, especially lymphoid cells, as in MDS patients.
In addition, the proportion of healthy and abnormal blood cells was similar in the mice as it was in the MDS patients, suggesting that the MDS bone marrow stem cells may not grow faster than normal stem cells.
Moreover, this technique for transplanting MDS stem cells into mice provides a method for testing new MDS therapies in patient samples prior to testing them in patients.
For more information, please see abstract 789 at the ASH 2011 meeting website.
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