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Aberrant levels of SUV39H1 and SUV39H2 methyltransferase are associated with genomic instability in chronic lymphocytic leukemia
Author(s) -
Carvalho AlvesSilva Juliana,
do Amaral Rabello Doralina,
Oliveira Bravo Martha,
LucenaAraujo Antônio,
Madureira de Oliveira Diego,
Morato de Oliveira Fábio,
Magalhaes Rego Eduardo,
PittellaSilva Fábio,
SaldanhaAraujo Felipe
Publication year - 2017
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.22128
Subject(s) - chronic lymphocytic leukemia , biology , chromosome instability , telomerase , genome instability , telomere , dna methylation , cancer research , genetics , leukemia , microbiology and biotechnology , gene expression , gene , chromosome , dna damage , dna
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 h TERT are associated with genomic instability of CLL. SUV39H (1/2) , SUV420H (1/2), and h TERT 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 h TERT expression. Furthermore, h TERT 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. Environ. Mol. Mutagen. 58:654–661, 2017. © 2017 Wiley Periodicals, Inc.