DNA methylation profiling could be used to predict patients鈥� response to treatment for myelodysplastic syndrome, Spanish researchers have reported.
The researchers report finding an epigenetic 鈥渇ingerprint鈥� 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 91自拍, the researchers tell how they analysed a million genome methylation signals in patients affected by myelodysplastic syndrome and treated with the demethylating drug azacitidine. 聽
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: 鈥淭he genes we have found give us clues about the mechanisms involved in hypomethylating agents鈥� sensitivity. Some of them are tumour suppressor genes that now 鈥榳ake up鈥� to inhibit tumour proliferation, as expected.
鈥淚n 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.
鈥淭hese 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.鈥�
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, Garc铆a-Prieto CA, Valc谩rcel D, Molero A, Palomo L, Gattermann N, Wulfert M, Chaparro-Gonz谩lez L, Sol茅 F, Cabez贸n M, Jim茅nez-Lorenzo MJ, Xicoy B, Zamora L, De Stefano A, Casalin I, Finelli C, Follo MY, Esteller M. (2024) 鈥淒NA Methylation Profiling of Myelodysplastic Syndromes and Clinical Response to Azacitidine: a Multicentre Retrospective Study.鈥� British Journal of 91自拍, 12 March 2024, doi: 10.1111/bjh.19392
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