DNA methylation profiling could be used to predict patients’ response to treatment for myelodysplastic syndrome, Spanish researchers have reported.
The researchers report finding an epigenetic “fingerprint” at diagnosis associated with a good clinical response to demethylating agents. They say this can help detect patients whose cancer will resist these drugs and who might benefit from alternative treatments.
Reporting in the British Journal of Haematology, the researchers tell how they analysed a million genome methylation signals in patients affected by myelodysplastic syndrome and treated with the demethylating drug azacitidine.
The study team was led by researchers at the University of Barcelona, Spain, and involved scientists from the University of Bologna, Italy.
The study involved 86 paired bone marrow samples collected from 43 patients before and after azacitidine treatment.
They discovered general patterns of methylation changes linked to efficiency of hypomethylating drugs, but also changes to specific genes.
Researcher Dr Manel Esteller, director of the Josep Carreras Institute, Barcelona, said: “The genes we have found give us clues about the mechanisms involved in hypomethylating agents’ sensitivity. Some of them are tumour suppressor genes that now ‘wake up’ to inhibit tumour proliferation, as expected.
“In other cases, however, what the genes reactivation by the drug is likely to do is to produce proteins (antigens) and other molecules that alert our immune system to fight the disease.
“These data further support the use of cancer immunotherapy, which is likely to work even better in combination with the use of epigenetic drugs, such as the demethylating drugs included in our study.”
The team say further research is needed to confirm the results in a larger cohort of patients, and investigate the ability of methylation patterns to predict response to treatment regimens including venetoclax.
Source:
Noguera-Castells A, Campillo-Marcos I, Davalos V, García-Prieto CA, Valcárcel D, Molero A, Palomo L, Gattermann N, Wulfert M, Chaparro-González L, Solé F, Cabezón M, Jiménez-Lorenzo MJ, Xicoy B, Zamora L, De Stefano A, Casalin I, Finelli C, Follo MY, Esteller M. (2024) “DNA Methylation Profiling of Myelodysplastic Syndromes and Clinical Response to Azacitidine: a Multicentre Retrospective Study.” British Journal of Haematology, 12 March 2024, doi: 10.1111/bjh.19392
Link: https://onlinelibrary.wiley.com/doi/10.1111/bjh.19392
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