title: Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes: genetic and epigenetic interactions.
abstract: Polo-like kinase 2 (SNK/PLK2), a transcriptional target for wild-type p53 and is hypermethylated in a high percentage of multiple myeloma and B cell lymphomas patients. Given these data, we sought to study the methylation status of the specific gene in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), and to correlate it with clinical and genetic features. Using methylation-specific PCR MSP, we analyzed the methylation profile of 45 cases of AML and 43 cases of MDS. We also studied the distribution of MTHFR A1298C and MTHFR C677T polymorphisms and FLT3 mutations in AML patients and correlated the results with hypermethylation in the SNK/PLK2 CpG island. The SNK/PLK2 CpG island was hypermethylated in 68.9% and 88.4% of AML and MDS cases, respectively. Cases with hypermethylation had a trend towards more favorable overall survival (OS). There was no association between different MTHFR genotypes and susceptibility to develop AML. SNK/PLK2 hypermethylation combined with the MTHFR AA1298 genotype was associated with a tendency for a better OS. Similarly, patients with SNK/PLK2 hypermethylation combined with the MTHFR CT677 polymorphism had a better OS (HR = 0.34; p = 0.017). SNK/PLK2 methylation associated with unmutated FLT3 cases had a trend for better OS compared to patients with mutated FLT3 gene. SNK/PLK2 is a novel epigenetically regulated gene in AML and MDS, and methylation occurs at high frequency in both diseases. As such, SNK/PLK2 could represent a potential pathogenetic factor, although additional studies are necessary to verify its exact role in disease pathogenesis.
authors.affiliation: Department of Hematology, University Hospital of Ioannina, Niarchos Avenue, 45500 Ioannina, Greece. benetatosleon@yahoo.com
authors.forename: Leonidas
authors.initials: L
authors.lastname: Benetatos
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Dasoula
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Hatzimichael
authors.forename: Nelofer
authors.initials: N
authors.lastname: Syed
authors.forename: Maria
authors.initials: M
authors.lastname: Voukelatou
authors.forename: George
authors.initials: G
authors.lastname: Dranitsaris
authors.forename: Konstantinos L
authors.initials: KL
authors.lastname: Bourantas
authors.forename: Tim
authors.initials: T
authors.lastname: Crook
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D004843:Epistasis, Genetic / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
chemical_list: C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases