Repetitive genomic elements and overall DNA methylation changes in acute myeloid and childhood B-cell lymphoblastic leukemia patients.
Aberrant epigenetic regulation is a hallmark of neoplastic cells. Increased DNA methylation of individual genes' promoter regions and decreases in overall DNA methylation level are both generally observed in cancer. In solid tumors, this global DNA hypomethylation is related to reduced methylation of repeated DNA elements (REs) and contributes to genome instability. The aim of the present study was to assess methylation level of LINE-1 and ALU REs and total 5-methylcytosine (5metC) content in adult acute myeloid leukemia (AML) (n = 58), childhood B-cell acute lymphoblastic leukemia (ALL) (n = 32), as the most frequent acute leukemias in two age categories and in normal adult bone marrow and children's blood samples. DNA pyrosequencing and ELISA assays were used, respectively. Global DNA hypomethylation was not observed in leukemia patients. Results revealed higher DNA methylation of LINE-1 in AML and ALL samples compared to corresponding normal controls. Elevated methylation of ALU and overall 5metC level were also observed in B-cell ALL patients. Differences of REs and global DNA methylation between AML cytogenetic-risk groups were observed, with the lowest methylation levels in intermediate-risk/cytogenetically normal patients. B-cell ALL is characterized by the highest DNA methylation level compared to AML and controls and overall DNA methylation is correlated with leukocyte count.
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, W.K. Roentgena 5, 02-781, Warsaw, Poland, mbujko@coi.waw.pl.
Mateusz
M
Bujko
Ewa
E
Musialik
Rafał
R
Olbromski
Marta
M
Przestrzelska
Marta
M
Libura
Anna
A
Pastwińska
Przemysław
P
Juszczyński
Lech
L
Zwierzchowski
Paweł
P
Baranowski
Janusz Aleksander
JA
Siedlecki
D000293:Adolescent; D020087:Alu Elements; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D042822:Genomic Instability; D006801:Humans; D007223:Infant; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data