Title:	Aberrant levels of SUV39H1 and SUV39H2 methyltransferase are associated with genomic instability in chronic lymphocytic leukemia
Authors:	Silva, Juliana Carvalho Rocha Alves da Silva Ramos, Doralina do Amaral Rabello Bravo, Martha Oliveira Araujo, Antônio Lucena Oliveira, Diego Madureira de Oliveira, Fábio Morato de Rêgo, Eduardo Magalhães Pittella-Silva, Fabio Araújo, Felipe Saldanha de
metadata.dc.contributor.affiliation:	Universidade de Brasília, Faculdade de Ciências da Saúde, Laboratório de Patologia Molecular do Câncer Universidade de Brasília, Faculdade de Ciências da Saúde, Laboratório de Patologia Molecular do Câncer Universidade de Brasília, Faculdade de Ciências da Saúde, Laboratório de Farmacologia Molecular Universidade Federal de Pernambuco, Laboratório de Hematologia Universidade de Brasília, Faculdade de Ciências da Saúde, Laboratório de Patologia Molecular do Câncer Universidade de São Paulo, Laboratório de Hematologia
Assunto::	Leucemia Cromossomos - anomalias Telomerase Metiltransferases
Issue Date:	2017
Publisher:	Wiley
Citation:	ALVES‐SILVA, Juliana Carvalho et al. Aberrant levels of SUV39H1 and SUV39H2 methyltransferase are associated with genomic instability in chronic lymphocytic leukemia. Environmental and Molecular Mutagenesis, v. 58, n. 9, p. 654-661, 2017. DOI: http://dx.doi.org/10.1002/em.22128. Acesso em: 03 out. 2022.
Abstract:	Chromosomal alterations are commonly detected in patients with chronic lymphocytic leukemia (CLL) and impact disease pathogenesis, prognosis, and progression. Telomerase expression (hTERT), its activity and the telomere length are other important predictors of survival and multiple outcomes in CLL. SUV39H and SUV420H enzymes are histone methyltransferases (HMTases) involved in several cellular processes, including regulation of telomere length, heterochromatin organization, and genome stability. Here, we investigated whether SUV39H1, SUV39H2, SUV420H1, SUV420H2, and hTERT are associated with genomic instability of CLL. SUV39H (1/2), SUV420H (1/2), and hTERT expression was determined in 59 CLL samples by real time PCR. In addition, ZAP-70 protein expression was evaluated by Flow Cytometry and patients’ karyotype was defined by Cytogenetic Analysis. Low expression of SUV39H1 was associated with the acquisition of altered and complex karyotypes. Conversely, high expression of SUV39H2 correlated with cytogenetic abnormalities in CLL patients. The pattern of karyotypic alterations differed in samples with detectable or undetectable hTERT expression. Furthermore, hTERT expression in CLL showed a correlation with transcript levels of SUV39H2, which, in part, can explain the association between SUV39H2 expression and cytogenetic abnormalities. Moreover, SUV39H1 correlated with SUV420H1 expression while SUV420H2 was associated with all other investigated HMTases. Our data show that the differential expression of SUV39H1 and SUV39H2 is associated with genomic instability and that the modulation of these HMTases can be an attractive approach to prevent CLL evolution.
DOI:	http://dx.doi.org/10.1002/em.22128
metadata.dc.relation.publisherversion:	https://onlinelibrary.wiley.com/doi/10.1002/em.22128
Appears in Collections:	Artigos publicados em periódicos e afins

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