5hmC: 5-hydroxymethylcytosine, 5mC: 5-methylcytosine, ADMA: asymmetric dimethylarginine, AML: acute myeloid leukemia, ALCL: anaplastic large cell lymphoma, ALK: anaplastic lymphoma kinase, ALL: acute lymphoblastic leukemia, APL: acute promyelocytic leukemia, ARID1A: AT-rich interactive domain-containing protein 1A, ARP5: actin-related protein 5, ATRA: all-trans retinoic acid, BAF: BRG/BRM-associated factor, Bcl-2: B-cell lymphoma 2, BCR: breakpoint cluster region, BET: bromodomain and extra terminal family, BIK: Bcl-2-interacting killer, BRD: bromodomain, BRG1: Brahma-related gene 1, BRM: Brahma, CAR: chimeric antigen receptor, CBP: CREB binding protein, ccRCC: clear cell renal cell carcinoma, CD: chromodomain, C/EBPα: CCAAT/enhancer-binding protein alpha, CHD: chromodomain-helicase DNA binding protein 5, CNS: central nervous system, CR: complete remission, CTCF: CCCTC-binding factor, DIPG: diffuse intrinsic pontine glioma, DOT1L: disruptor of telomeric silencing 1-like, DNMT: DNA methyltransferase, ERK: extracellular signal-regulated kinase, FDA: Food and Drug Administration, EBV: Epstein-Barr virus, EHMT2: euchromatic histone lysine methyltransferase 2, ERα: estrogen receptor α, EZH2: enhancer of zeste homolog 2, FOXO1: forkhead box protein O1, GCN5: general control non-depressible 5, G-CSF: granulocyte colony-stimulating factor, GD2: disialoganglioside 2, GNAT: GCN5-related N-acetyltransferase, HAT: histone acetyltransferase, HDAC: histone deacetylase, HMA: hypomethylating agents, HSCT: hematopoietic stem cell transplantation, IDH: isocitrate dehydrogenase, IL-6: interleukin 6, INO80: inositol-requiring mutant 80, ISWI: imitation SWI, JAK: Janus kinase, JARID1A: Jumonji AT-rich interactive domain 1A, JHDM: JmjC domain-containing histone demethylase enzyme, JmjC: Jumonji C domain, JMML: juvenile myelomonocytic leukemia, KDM: histone lysine demethylase, KMT: histone lysine-specific methyltransferase, LSD1: lysine-specific demethylase 1, MBD: methyl-CpG-binding domain, MBP: methyl-binding protein, MDS: myelodysplastic syndrome, MeCP2: methyl CpG binding protein 2, MDM2: mouse double minute 2 homolog, MLL: mixed lineage leukemia, MMA: monomethyl arginine, MOZ: monocytic leukemia zinc finger protein, MRD: minimal residual disease, MYST: Moz, Ybf2, Sas2 and Tip60, NHL: non-Hodgkin lymphoma, NFκB: nuclear factor kappa light chain enhancer of activated B cells, NK: natural killer cell, NPM1: nucleophosmin 1, NSD: nuclear receptor binding SET domain protein, NUP98: nucleoporin 98, OPC: oligodendrocyte precursor cell, OS: overall survival, PAX3: paired box gene 3, PCAF: p300/CBP-associated factor, PD1: programmed cell death 1, PHD: plant homeodomain, PHF6: plant homeodomain finger 6, PRMT: protein arginine methyltransferase, PTM: posttranslational modification, PWWP: proline-tryptophan-tryptophan-proline domain, R/R: relapsed or refractory, RASSF1A: Ras association domain-containing protein 1 isoform A, RFS: relapse-free survival, RIG-I: retinoic acid-inducible gene I, SAHA: suberoylanilide hydroxamic acid, SCID: severe combined immunodeficiency, SDMA: symmetric dimethylarginine, SHH: sonic hedgehog, SIRT: sirtuin, SMARC: SWI/SNF-related matrix associated actin dependent regulator of chromatin, SRA: SET and RING associated domain, STAT: signal transducer and activator of transcription, SUV39H1: suppressor of variegation 3-9 homolog 1, SWI/SNF: switch/sucrose nonfermenting, TFAP2A: transcription factor AP-2 alpha, TET: ten eleven translocation, TGFβ: transforming growth factor-β, UHRF: ubiquitin-like, containing PHD and RING finger domains, UTX: ubiquitously transcribed tetratricopeptide repeat, X chromosome, YEATS: Yaf9 ENL AF9 Taf14 Sas5, WDR: WD40 repeat.

Figure 1. Epigenetic agents in the landscape of personalized anticancer treatment.

Figure 1. Epigenetic agents in the landscape of personalized anticancer treatment.

Figure 2. Reader molecules as novel therapeutic targets in pediatric malignancies (see references in the text). Abbreviations of diseases: ALCL: anaplastic large cell lymphoma, ALL: acute lymphoblastic leukemia, AML: acute myeloid leukemia, ATRT: atypical teratoid rhabdoid tumor, ccRCC: clear cell renal cell carcinoma, GBM: glioblastoma multiforme, MB: medulloblastoma.

Figure 2. Reader molecules as novel therapeutic targets in pediatric malignancies (see references in the text). Abbreviations of diseases: ALCL: anaplastic large cell lymphoma, ALL: acute lymphoblastic leukemia, AML: acute myeloid leukemia, ATRT: atypical teratoid rhabdoid tumor, ccRCC: clear cell renal cell carcinoma, GBM: glioblastoma multiforme, MB: medulloblastoma.

Figure 3. Targetable components of nucleosome remodeling complexes in pediatric malignancies (see references in the text). Abbreviations of diseases: AML: acute myeloid leukemia, GBM: glioblastoma multiforme, NB: neuroblastoma, RMS: rhabdomyosarcoma.

Figure 3. Targetable components of nucleosome remodeling complexes in pediatric malignancies (see references in the text). Abbreviations of diseases: AML: acute myeloid leukemia, GBM: glioblastoma multiforme, NB: neuroblastoma, RMS: rhabdomyosarcoma.

Table 1. Examples for epigenetic biomarkers in the differential diagnosis, prognosis and chemoresistance prediction of malignant diseases (see references in the text).

Table 1. Examples for epigenetic biomarkers in the differential diagnosis, prognosis and chemoresistance prediction of malignant diseases (see references in the text).

DiagnosisPrognosisChemoresistance PredictionDNA-methylation profileT-LBL, pilocytic spinal cord astrocytoma, retinoblastomaJMML, adrenocortical tumorsPlatinum chemotherapy (various cancers)TET2 AML 5hmC patternMetastatic neuroblastomaAML, grade II astrocytoma SIRT2 Cytosine arabinoside and daunorubicin (AML)SIRT6 Hodgkin lymphoma EZH2 MDS, ependymomaTemozolomide (GBM)DOT1L ccRCC SETD2 MDS NUP98/NSD1 fusion AML

Table 2. Targeted epigenetic interventions in hematological malignancies and solid tumors (see references in the text).

Table 2. Targeted epigenetic interventions in hematological malignancies and solid tumors (see references in the text).

Epigenetic ProcessEnzyme FamilyEnzyme SubfamilyEnzymeAgentHematological MalignanciesSolid TumorsDNA methylationDNMT DNMT1,3Azacitidine, decitabineMDS, AML, JMML, CMML, ALCLGBM, neuroblastoma, RMS, synovial src, ccRCC, osteosarcoma, Ewing src, RTDNA hydroxymethylationTET TET1,2 Bobcat339 T-ALLMedulloblastoma, osteosarcomaHistone acetylationHAT PU139 (pan-inhibitor) Neuroblastoma p300/CBPp300, CBP MDS MYSTMOF (MYST1) NUP98-HOXA9-driven AML HBO (MYST2) WM-3835 Osteosarcoma TIP60 Osteosarcoma GNATGCN5 Pre-B ALL, non-APL AML, Burkitt lymphoma PCAF Alveolar RMSHistone deacetylationHDACHDAC I, IIa, Iib, IVHDAC 1-11 BelinostatAPLRetinoblastoma HDAC1i Hepatoblastoma HDAC6iBurkitt lymphomagr3 medulloblastoma, RMS, Ewing src I13t(8;21) AML, MLL-rearranged AML MocetinostatMLL-AF9Glioma PanobinostatR/R AML, relapsed cHL, t(4;11)-positive infant ALLSoft tissue sarcoma, Wilms’ tumor RomidepsinBurkitt lymphoma, t(4;11)-positive infant ALLNeuroblastoma Spiruchostatin A Neuroblastoma Trichostatin At(4;11)-positive infant ALLMedulloblastoma Vorinostat/SAHAR/R AML, t(4;11)-positive infant ALLMedulloblastoma, glioma, grC ependymomaHistone deacylationSIRT SIRT1Tenovin 6, EX527ALL, t(8;21) AML, MDS, Burkitt lymphomaGlioma, soft tissue src, Ewing src SIRT2Tenovin 6ALLSoft tissue src SIRT3 GBM SIRT4 Neuroblastoma, ccRCC SIRT5NRD167AML SIRT6 Neuroblastoma, ccRCC, nasopharyngeal cc SIRT7 GliomaHistone Lys methylationKMT SET-domainEZH2DZNep, tazemetostat (EPZ-6438), GSK343, EPZ005687MDS, ALL, monocytic AML, NHLSHH medulloblastoma, neuroblastoma, H3K27M gliomas, epithelial src, RMS, RT G9a (EHMT2) BIX01294 ALLNeuroblastoma, embryonal RMS, Ewing src NSD1 AML with t(5;11) translocation SUV39H1 Astrocytoma, high-grade glioma, ccRCC w/o SET domainDOT1LPinometostat (EPZ5676)MLL-r AML, DNMT3A-mutant AMLNeuroblastoma, retinoblastomaHistone Arg methylationPRMT AMI-1 and SAH (pan-inhibitors) RMS PRMT128dFLT3-ITD AML, MLL-r ALLMedulloblastoma PRMT5 NHLSHH medulloblastoma PRMT6 EPZ020411 GBMHistone demethylationKDM1 LSD1 (KDM1A)FY56, S2157, HCI2509, SP2509AML, T-ALL (CNS)Ewing src, retinoblastoma JHDM KDM3A (JHDM2A) RMS, osteosarcoma KDM3C (JMJD1C)JDI-10MLL-r AML KDM4A (JMJD2A)SD49-7LSC KDM4B (JMJD2B) Alveolar RMS KDM5A (JARID1A) APL KDM5B (JARID1B) AS-8351 Ewing src KDM6A (UTX) GSKJ4 AML KDM6B (JMJD3) GSKJ4 AML JMJD6 ccRCC