Myelodysplastic syndromes linked to abnormal stem cells
Washington: Abnormal bone marrow stem cells can drive the development of myelodysplastic syndromes (MDS), a group of blood disorders that often leads to acute leukaemia in elderlies, scientists have claimed.
The findings, published in the journal Blood, could yield targeted therapies against MDS as well as several MDS-related cancers, researchers at Albert Einstein College of Medicine of Yeshiva University said.
"Researchers have suspected that MDS is a `stem cell disease` and now we finally have proof," said co-senior author Amit Verma, associate professor of medicine and molecular biology at Einstein.
"Equally important, we found that even after MDS standard treatment, abnormal stem cells persist in the bone marrow. So, although the patient may be in remission, those stem cells don`t die and the disease will inevitably return," he said.
"Based on our findings, it`s clear that we need to wipe out the abnormal stem cells in order to improve cure rates."
MDS are a diverse group of incurable diseases that affect the bone marrow and lead to low numbers of blood cells. While some forms of MDS are mild and easily managed, some 25 to 30 per cent of cases develop into an aggressive cancer called acute myeloid leukaemia.
Most cases of MDS, which affects over 15,000 people every year in the US alone, generally occur in people over 60 years, but it can affect people of any age and is more common in men than women. Treatment usually involves chemotherapy to destroy abnormal blood cells along with supportive care such as blood transfusions.
In the new study, lead author Britta Will and colleagues analysed bone marrow stem cells and progenitor cells (or cells formed by stem cells) from 16 patients with various types of MDS and 17 healthy controls.
The stem and progenitor cells were isolated from bone marrow using novel cell-sorting methods developed in the laboratory. Genome-wide analysis revealed widespread genetic and epigenetic alterations in stem and progenitor cells taken from MDS patients, in comparison to cells taken from healthy controls. The abnormalities were more pronounced in patients with types of MDS likely to prove fatal than in patients with lower-risk types.
"Our study offers hope that MDS can be more effectively treated, with therapies that specifically target genes that are deregulated in early stem and progenitor cells," co-author Dr Ulrich Steidl said.
"In addition, our findings could help to detect minimal residual disease in patients in remission, allowing for more individualised treatment strategies that permanently eradicate the disease," Dr Steidl added.
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