P052 Acquired mutations in TET2 are common in myelodysplastic syndromes

Langemeijer, Saskia; Kuiper, Roland P.; Berends, Marieke; Knops, Ruth; Aslanyan, Mariam G; Massop, Marion; Hoogen, Patricia van den; Kessel, Ad Geurts van; Raymakers, R.A.P.; Verburgh, Estelle; Hagemeijer, Anne; Vandenberghe, Peter; Witte, T. de; Reijden, Bert van der; Jansen, J.

doi:10.1016/s0145-2126(09)70132-8

Cited by 5 publications

(2 citation statements)

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“…Importantly, the prognostic value of the TET2 mutations remains controversial. In MDS, one study showed a correlation between TET2 mutations and a more favorable prognosis, while other studies showed no impact of TET2 mutations on the prognosis in MDS and AML (153)(154)(155) or even an inverse correlation (156). For MM, no prognostic potential was shown for TET2 mutations on its own, but Pawlyn et al found that mutations in any of the DNA methylation modifiers (TET1/2/ 3, IDH1/2 or DNMT1/3A/B) correlated with a shorter OS (87).…”

Section: • Dnmt3bmentioning

confidence: 99%

Aberrant DNA methylation in multiple myeloma: A major obstacle or an opportunity?

Muylaert

Hemelrijck²,

Maes³

et al. 2022

Front. Oncol.

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Drug resistance (DR) of cancer cells leading to relapse is a huge problem nowadays to achieve long-lasting cures for cancer patients. This also holds true for the incurable hematological malignancy multiple myeloma (MM), which is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Although new treatment approaches combining immunomodulatory drugs, corticosteroids, proteasome inhibitors, alkylating agents, and monoclonal antibodies have significantly improved median life expectancy, MM remains incurable due to the development of DR, with the underlying mechanisms remaining largely ill-defined. It is well-known that MM is a heterogeneous disease, encompassing both genetic and epigenetic aberrations. In normal circumstances, epigenetic modifications, including DNA methylation and posttranslational histone modifications, play an important role in proper chromatin structure and transcriptional regulation. However, in MM, numerous epigenetic defects or so-called ‘epimutations’ have been observed and this especially at the level of DNA methylation. These include genome-wide DNA hypomethylation, locus specific hypermethylation and somatic mutations, copy number variations and/or deregulated expression patterns in DNA methylation modifiers and regulators. The aberrant DNA methylation patterns lead to reduced gene expression of tumor suppressor genes, genomic instability, DR, disease progression, and high-risk disease. In addition, the frequency of somatic mutations in the DNA methylation modifiers seems increased in relapsed patients, again suggesting a role in DR and relapse. In this review, we discuss the recent advances in understanding the involvement of aberrant DNA methylation patterns and/or DNA methylation modifiers in MM development, progression, and relapse. In addition, we discuss their involvement in MM cell plasticity, driving myeloma cells to a cancer stem cell state characterized by a more immature and drug-resistant phenotype. Finally, we briefly touch upon the potential of DNA methyltransferase inhibitors to prevent relapse after treatment with the current standard of care agents and/or new, promising (immuno) therapies.

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Section: • Dnmt3bmentioning

confidence: 99%

Aberrant DNA methylation in multiple myeloma: A major obstacle or an opportunity?

Muylaert

Hemelrijck²,

Maes³

et al. 2022

Front. Oncol.

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“…In addition to heritable disease-causing mutations, random or induced DNA alterations may appear in somatic cells after birth and may result in severe illness, such as some cancer types [64,65]. In these cases, the "causative mutation" need not be one mutation but can be represented by several mutations [66].…”

Section: Discussionmentioning

confidence: 99%

Detecção de variações genômicas em bovinos da raça nelore usando dados de genotipagem e ressequenciamento

Silva¹

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Foram aproximadamente três anos e meio de muito estudo e debates. Por fim, fica difícil agradecer a todos aqueles que participaram da construção desta tese de forma direta ou indireta. Portanto, irei mencionar alguns nomes e, ao mesmo tempo, estender meus profundos cumprimentos a todas as pessoas que me ajudaram.Primeiramente, agradeço a Deus por permitir a conclusão de mais uma etapa da minha vida científica e à minha esposa, Karina de Cassia Faria, por me oferecer condições para que eu pudesse estudar e tornar-me doutor. Compartilhamos cada momento de alegria e de angústia nesses últimos anos. Não posso deixar de mencionar meu filho, Thomas Faria da Silva, que sofria com a minha ausência e a cada despedida.Ao meu orientador e amigo, Michel Eduardo Beleza Yamagishi, que é um grande cientista com ideias fantásticas. Além de ser quem me incentivou à ir para a Unicamp fazer este doutorado. Obrigado pela atenção, paciência ao lidar com os problemas e pelo exemplo de profissionalismo. Não existem palavras suficientes para agradecer a oportunidade e para expressar a minha gratidão.Ao meu coorientador e amigo, Alexandre Rodrigues Caetano, um excelente pesquisador: obrigado por me apresentar à bovinocultura e pela disponibilidade para nossas conversas para alinhamento da tese e artigos.Ao meu médico José Eduardo Neves e toda a sua equipe. Graças à sua competência hoje não estou na fila de um transplante de rins.Aos meus grandes amigos e agregados da república Rasputin pela convivência harmoniosa e intensa. Um agradecimento especial aos meus grandes amigos Danilo, José Henrique, Paulo, Bruno, Finado, Saulo, Bob e Renan: obrigado pela amizade, pela força nas horas difíceis, e pela alegria compartilhada ao ver o desenvolvimento deste trabalho e o seu término.Aos amigos da EMBRAPA, em especial aqueles que trabalham no Laboratório

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CXXC4 mRNA levels are associated with clinicopathological parameters and survival of myelodysplastic syndrome patients

Fan

Zhao

et al. 2014

Leukemia Research

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P052 Acquired mutations in TET2 are common in myelodysplastic syndromes

Cited by 5 publications

References 0 publications

Aberrant DNA methylation in multiple myeloma: A major obstacle or an opportunity?

Aberrant DNA methylation in multiple myeloma: A major obstacle or an opportunity?

Detecção de variações genômicas em bovinos da raça nelore usando dados de genotipagem e ressequenciamento

CXXC4 mRNA levels are associated with clinicopathological parameters and survival of myelodysplastic syndrome patients

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