title: Restriction landmark genome scanning for aberrant methylation in primary refractory and relapsed acute myeloid leukemia; involvement of the WIT-1 gene.
abstract: There is substantial evidence to suggest that aberrant DNA methylation in the regulatory regions of expressed genes may play a role in hematologic malignancy. In the current report, the Restriction Landmark Genomic Scanning (RLGS) method was used to detect aberrant DNA methylation (M) in acute myeloid leukemia (AML). RLGS-M profiles were initially performed using DNA from diagnostic, remission, and relapse samples from a patient with AML. Rp18, one of the eight spots found that was absent in the relapse sample, was cloned. Sequence analysis showed that the spot represented a portion of the WIT-1 gene on human chromosome 11p13. Rp18 was missing in the relapse sample due to a distinct DNA methylation pattern of the WIT-1 gene. Twenty-seven AML patients that entered CR after therapy (i.e., chemosensitive) were studied and only 10 (37%) of the diagnostic bone marrow (BM) samples showed methylation of WIT-1. However, seven of eight (87.5%) diagnostic BM samples from primary refractory AML (chemosensitive) showed methylation of WIT-1. The incidence of WIT-1 methylation in primary refractory AML was significantly higher than that noted in chemosensitive AML (P=0.018). Together, these results indicate that RLGS-M can be used to find novel epigenetic alterations in human cancer that are undetectable by standard methods. In addition, these results underline the potential importance of WIT-1 methylation in chemoresistant AML.
authors.affiliation: Department of Microbiology and Immunology, Comprehensive Cancer Center, The Ohio State University, Columbus 43210, USA.
authors.forename: C
authors.initials: C
authors.lastname: Plass
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: M P
authors.initials: MP
authors.lastname: Strout
authors.forename: W
authors.initials: W
authors.lastname: El-Rifai
authors.forename: E
authors.initials: E
authors.lastname: Elonen
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
authors.forename: G
authors.initials: G
authors.lastname: Marcucci
authors.forename: D C
authors.initials: DC
authors.lastname: Young
authors.forename: W A
authors.initials: WA
authors.lastname: Held
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D000208:Acute Disease; D015139:Blotting, Southern; D001854:Bone Marrow Cells / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D012008:Recurrence
chemical_list: D004273:DNA, Neoplasm