3 research outputs found
DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia
Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML)
pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures
with defined genomic rearrangements in acute myeloid leukemia are required.
Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we
validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated
with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1
was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced
in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures.
To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/
progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying
the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the
MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the
epigenetic signature observed in the patients.
Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers
for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the
methylation signatur
DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia
Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML)
pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures
with defined genomic rearrangements in acute myeloid leukemia are required.
Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we
validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated
with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1
was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced
in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures.
To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/
progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying
the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the
MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the
epigenetic signature observed in the patients.
Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers
for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the
methylation signatur