AI Article Synopsis

  • Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed cancer in children under 15, and it involves significant genetic and epigenetic changes, particularly in DNA methylation patterns.
  • Research identified over 25,000 differentially methylated regions (DMRs) in ALL patients, primarily affecting gene expression related to key cellular functions such as transcription, apoptosis, and proliferation.
  • Key genes implicated in ALL, including potential epi-driver genes, exhibit altered expression due to aberrant methylation, highlighting the critical role of epigenetic modifications in the development of this leukemia.

Article Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 15. In addition to genetic aberrations, epigenetic modifications such as DNA methylation are altered in cancer and impact gene expression. To identify epigenetic alterations in ALL, genome-wide methylation profiles were generated using the methylated CpG island recovery assay followed by next-generation sequencing. More than 25,000 differentially methylated regions (DMR) were observed in ALL patients with ∼ 90% present within intronic or intergenic regions. To determine the regulatory potential of the DMR, whole-transcriptome analysis was performed and integrated with methylation data. Aberrant promoter methylation was associated with the altered expression of genes involved in transcriptional regulation, apoptosis, and proliferation. Novel enhancer-like sequences were identified within intronic and intergenic DMR. Aberrant methylation in these regions was associated with the altered expression of neighboring genes involved in cell cycle processes, lymphocyte activation and apoptosis. These genes include potential epi-driver genes, such as SYNE1, PTPRS, PAWR, HDAC9, RGCC, MCOLN2, LYN, TRAF3, FLT1, and MELK, which may provide a selective advantage to leukemic cells. In addition, the differential expression of epigenetic modifier genes, pseudogenes, and non-coding RNAs was also observed accentuating the role of erroneous epigenetic gene regulation in ALL.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622668PMC
http://dx.doi.org/10.1080/15592294.2015.1078050DOI Listing

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