Way to prevent myelodysplastic syndrome progression

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Way to prevent myelodysplastic syndrome progression

Postby whbio » Mar 29 2017 4:06 pm

A paper in the journal Leukemia now provides a way to prevent myelodysplastic syndrome (MDS) from developing into a more aggressive cancer.

MDS is a group of diseases in which the bone marrow does not produce enough healthy blood cells. The disease primarily affects the elderly but can also affect young people. In MDS, stem blood cells in the bone marrow do not mature and become healthy blood cells, resulting in low levels of mature blood cells in the bloodstream. Common symptoms include anemia, fatigue, frequent infections, and easy bleeding. Some cases of MDS can be easily managed but other cases can be life-threatening.

Roughly 30% of MDS patients will eventually develop a form of cancer called acute myeloid leukemia (AML). For this reason, MDS is sometimes referred to as a pre-leukaemic disorder. AML often progresses rapidly and is very hard to treat. Now a study appearing in the journal Leukemia reveals that a protein called p300 can prevent MDS from developing into AML. The study is led by Stephen Nimer at Sylvester Comprehensive Cancer Center.

Nimer has been studying MDS for many years. For the current study, Nimer and colleagues looked at the role of the p300 protein in MDS. When they deleted p300 in mouse models, all the animals quickly developed leukemia. The finding is unexpected because it is thought that p300 may promote cancer under certain conditions.

p300 is an enzyme that functions as histone acetyltransferase, which increases gene transcription by adding an acetyl group to histone. p300 and its homolog CBP are transcriptional co-factors for many nuclear proteins, including MYC, p53 and E2F. Both p300 and CBP have been implicated in tumorigenesis. This study showed that loss of p300, but not CBP, significantly accelerated the onset of AML.

To determine p300’s function in MDS cells, the researchers cultured MDS cells in vitro but found that the cells were unable to grow well. However, when they deleted p300 in MDS cells, the cells grew much better. Moreover, even though p300 and CBP are highly homologous, they appeared to have non-redundant functions.

Taken together, the results suggest that p300 may be a tumor suppressor that inhibits progression of MDS to leukemia. Importantly, p300 has no apparent effect on healthy stem cells.

Currently, no treatment except chemotherapy can stop MDS from developing into AML. But there are some experimental drugs that can enhance the function of p300, and these drugs may have the potential to inhibit AML in MDS patients. By the way, Cusabio offers p300, CBP, and related antibodies. http://www.cusabio.com/
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