title: Importance of epigenetic changes in cancer etiology, pathogenesis, clinical profiling, and treatment: what can be learned from hematologic malignancies?
abstract: Epigenetic alterations represent a key cancer hallmark, even in hematologic malignancies (HMs) or blood cancers, whose clinical features display a high inter-individual variability. Evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-based, clinical and experimental studies, we hypothesize that factors associated with risk for developing a HM, such as metabolic syndrome and chronic inflammation, trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Among others, signaling pathways associated with such risk factors include pro-inflammatory nuclear factor κB (NF-κB), and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways, which include signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.
authors.affiliation: Laboratory of Cytometry, Institute of Molecular Genetics, CNR, University of Pavia, 27100 Pavia, Italy.
authors.forename: Lorella
authors.initials: L
authors.lastname: Vecchio
authors.forename: Paul Faustin
authors.initials: PF
authors.lastname: Seke Etet
authors.forename: Maulilio John
authors.initials: MJ
authors.lastname: Kipanyula
authors.forename: Mauro
authors.initials: M
authors.lastname: Krampera
authors.forename: Armel Hervé
authors.initials: AH
authors.lastname: Nwabo Kamdje
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D057890:Epigenomics; D020869:Gene Expression Profiling; D019337:Hematologic Neoplasms / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D006801:Humans