Epigenetic mechanisms and oral mucositis in children with acute lymphoblastic leukaemia

Author:

Guimarães Juliana Ramalho1ORCID,de Souza Beatriz Fernandes1ORCID,Filho José Maria Chagas Viana2ORCID,Damascena Lecidamia Cristina Leite3ORCID,Valença Ana Maria Gondim3ORCID,Persuhn Darlene Camati4ORCID,de Oliveira Naila Francis Paulo14ORCID

Affiliation:

1. Postgraduate Program in Dentistry Health Sciences Center Federal University of Paraíba, ‐ UFPB João Pessoa Paraíba Brazil

2. UNIESP University Center João Pessoa Brazil

3. Postgraduate Program in Decision Models and Health Center for Exact and Natural Sciences Federal University of Paraíba João Pessoa Paraíba Brazil

4. Department of Molecular Biology Center for Exact and Natural Sciences Federal University of Paraíba, ‐ UFPB João Pessoa Paraíba Brazil

Abstract

AbstractThis study aimed to investigate the relationship between epigenetic mechanisms and oral mucositis (OM) in paediatric patients with acute lymphoblastic leukaemia. Oral cells were collected from 76 participants, including 15 healthy individuals, 10 patients with acute lymphoblastic leukaemia but without a history of OM and 51 acute lymphoblastic leukaemia patients with a history of OM (35 with active OM and 16 who had recovered from OM). Global DNA methylation in the miR‐9‐1 and miR‐9‐3 genes was performed. Seven polymorphisms rs1801131, rs1801133 (MTHFR), rs2228611 (DNMT1), rs7590760, rs1550117 (DNMT3A), rs6087990, rs2424913 (DNMT3B) were genotyped and an analysis of association with global DNA methylation was performed. The global methylation levels were lower in cancer patients recovered from OM than in the other groups. A higher frequency of unmethylated profile for miR‐9‐1 and partially methylated profile for miR‐9‐3 was observed in cancer patients regardless of OM history compared to healthy patients. The GG genotype of the rs2228611 (DNMT1) polymorphism was associated with higher levels of global methylation in cancer patients irrespective of OM. It was concluded that global methylation is associated with mucosal recovery. The effect of DNMT1 genotype on the global DNA methylation profile, as well as the methylation profile of miR‐9‐1 and miR‐9‐3 in cancer patients is independent of OM.

Funder

Fundação de Apoio à Pesquisa do Estado da Paraíba

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Publisher

Wiley

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