# The role of epigenetic modifications in hematological cancers **Authors:** Jovana Ilic, Anna Bold, Stefan Knop PMC · DOI: 10.3389/fonc.2026.1744018 · Frontiers in Oncology · 2026-02-05 ## TL;DR This paper reviews how changes in epigenetic regulation contribute to the development and progression of blood cancers like leukemia and lymphoma. ## Contribution The paper provides a comprehensive review of epigenetic alterations in hematological cancers and their impact on oncogenesis. ## Key findings - Mutations in enzymes regulating DNA methylation and histone modifications are linked to chromatin changes in blood cancers. - Altered epigenetic mediators influence transcriptional profiles, promoting cancer progression and drug resistance. - Key epigenetic changes are identified in leukemias, lymphomas, and multiple myeloma. ## Abstract Epigenetic regulation of gene expression entails DNA methylation and histone modifications, which orchestrate chromatin structure and transcriptional activity. Aberrant regulation of these mechanisms contributes to the development and progression of hematological cancers. Mutations in enzymes mediating DNA methylation and histone modification patterns reshape chromatin structure, influencing transcriptional profiles, thus promoting oncogenesis, clonal evolution and drug resistance. This review focuses on significant alterations in DNA methylation patterns, mutations and changes in expression of histone modifying enzymes and chromatin remodeling complexes described in leukemias, lymphomas and multiple myeloma. We summarize the most prominent changes in epigenetic mediators and their impact on transcriptional activity and oncogenesis. ## Linked entities - **Diseases:** leukemias (MONDO:0005059), multiple myeloma (MONDO:0009693) ## Full-text entities - **Genes:** KDM1A (lysine demethylase 1A) [NCBI Gene 23028] {aka AIMAH3, AOF2, BHC110, CPRF, KDM1, LSD1}, TDG (thymine DNA glycosylase) [NCBI Gene 6996] {aka hTDG}, IGHD (immunoglobulin heavy constant delta) [NCBI Gene 3495], ALL1 (Leukemia, acute lymphocytic, susceptibility to, 1) [NCBI Gene 100310785], EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, SMARCA1 (SNF2 related chromatin remodeling ATPase 1) [NCBI Gene 6594] {aka ISWI, NURF140, SNF2L, SNF2L1, SNF2LB, SNF2LT}, CHD1L (chromodomain helicase DNA binding protein 1 like) [NCBI Gene 9557] {aka ALC1, CHDL}, SUV39H1 (SUV39H1 histone lysine methyltransferase) [NCBI Gene 6839] {aka H3-K9-HMTase 1, KMT1A, MG44, SUV39H}, MLLT3 (MLLT3 super elongation complex subunit) [NCBI Gene 4300] {aka AF9, YEATS3}, TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790] {aka IMD75, KIAA1546, MDS}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, IRF4 (interferon regulatory factor 4) [NCBI Gene 3662] {aka IMD131, LSIRF, MUM1, NF-EM5, SHEP8}, SMARCA5 (SNF2 related chromatin remodeling ATPase 5) [NCBI Gene 8467] {aka ISWI, SNF2H, WCRF135, hISWI, hSNF2H}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, TET1 (tet methylcytosine dioxygenase 1) [NCBI Gene 80312] {aka CXXC6, LCX, bA119F7.1}, CD34 (CD34 molecule) [NCBI Gene 947], SMARCA2 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2) [NCBI Gene 6595] {aka BAF190, BIS, BRM, NCBRS, SAMRCA2, SNF2}, ARID1A (AT-rich interaction domain 1A) [NCBI Gene 8289] {aka B120, BAF250, BAF250a, BM029, C1orf4, CSS2}, CHDH (choline dehydrogenase) [NCBI Gene 55349], HDAC1 (histone deacetylase 1) [NCBI Gene 3065] {aka GON-10, HD1, KDAC1, RPD3, RPD3L1}, HOXB13 (homeobox B13) [NCBI Gene 10481] {aka HPC9, PSGD}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 1789] {aka FSHD4, ICF, ICF1, M.HsaIIIB}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, NR0B2 (nuclear receptor subfamily 0 group B member 2) [NCBI Gene 8431] {aka SHP, SHP1}, BAZ2A (bromodomain adjacent to zinc finger domain 2A) [NCBI Gene 11176] {aka TIP5, WALp3}, CHD7 (chromodomain helicase DNA binding protein 7) [NCBI Gene 55636] {aka CRG, HH5, IS3, KAL5}, KMT2B (lysine methyltransferase 2B) [NCBI Gene 9757] {aka CXXC10, DYT28, HRX2, MLL1B, MLL2, MLL4}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, SRY (sex determining region Y) [NCBI Gene 6736] {aka SRXX1, SRXY1, TDF, TDY}, DNAH8 (dynein axonemal heavy chain 8) [NCBI Gene 1769] {aka ATPase, SPGF46, hdhc9}, NANOG (Nanog homeobox) [NCBI Gene 79923], CDKN2B (cyclin dependent kinase inhibitor 2B) [NCBI Gene 1030] {aka CDK4I, INK4B, MTS2, P15, TP15, p15INK4b}, CD14 (CD14 molecule) [NCBI Gene 929], HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, CBR1 (carbonyl reductase 1) [NCBI Gene 873] {aka CBR, PG-9-KR, SDR21C1, hCBR1}, CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387] {aka CBP, KAT3A, MKHK1, RSTS, RSTS1}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, HOXA9 (homeobox A9) [NCBI Gene 3205] {aka ABD-B, HOX1, HOX1.7, HOX1G}, BCL11B (BCL11 transcription factor B) [NCBI Gene 64919] {aka ATL1, ATL1-alpha, ATL1-beta, ATL1-delta, ATL1-gamma, CTIP-2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, KMT2A (lysine methyltransferase 2A) [NCBI Gene 4297] {aka ALL-1, ALL1, CXXC7, GAS7, HRX, HTRX}, TET3 (tet methylcytosine dioxygenase 3) [NCBI Gene 200424] {aka BEFAHRS, hCG_40738}, INO80 (INO80 complex ATPase subunit) [NCBI Gene 54617] {aka INO80A, INOC1}, CHD4 (chromodomain helicase DNA binding protein 4) [NCBI Gene 1108] {aka CHD-4, Mi-2b, Mi2-BETA, SIHIWES}, IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418] {aka D2HGA2, ICD-M, IDH, IDH-2, IDHM, IDP}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, CHD2 (chromodomain helicase DNA binding protein 2) [NCBI Gene 1106] {aka DEE94, EEOC}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, H2AC18 (H2A clustered histone 18) [NCBI Gene 8337] {aka H2A, H2A.2, H2A/O, H2A/q, H2AFO, H2a-615}, NSD2 (nuclear receptor binding SET domain protein 2) [NCBI Gene 7468] {aka KMT3F, KMT3G, MMSET, RAUST, REIIBP, TRX5}, CDKN1B (cyclin dependent kinase inhibitor 1B) [NCBI Gene 1027] {aka CDKN4, KIP1, MEN1B, MEN4, P27KIP1} - **Diseases:** CML (MESH:D015464), Hematological cancers (MESH:D009369), PTCL (MESH:D016411), MM (MESH:D009101), TET2 deficiency (MESH:D005171), B-CLL (MESH:D015451), myeloid diseases (MESH:D007951), myeloid malignancies:10 (MESH:C557827), natural killer/T-cell lymphoma (MESH:D000077428), blood cancers (MESH:D019337), MDS (MESH:D009190), AML (MESH:D015470), carcinogenesis (MESH:D063646), oncogenes (MESH:D000074723), Burkitt lymphoma (MESH:D002051), Hodgkin lymphoma (MESH:D006689), splenomegaly (MESH:D013163), toxicity (MESH:D064420), immature (MESH:D013724), -cell lineage malignancies (MESH:D015456), ALL (MESH:D054198), T-ALL (MESH:D054218), leukemia (MESH:D007938), metastasis (MESH:D009362), AITL (MESH:D016399), FL (MESH:D008224), CMML (MESH:D015477), MGUS (MESH:D008998), DLBCL (MESH:D016403), HAT dysfunction (MESH:D006331), B, T and NK-cell lymphomas (MESH:D016393), Lymphomas (MESH:D008223), APL (MESH:D015473) - **Chemicals:** enasidenib (MESH:C000605269), isocitrate (MESH:C034219), belinostat (MESH:C487081), 2-HG (MESH:C019417), ivosidenib (MESH:C000627630), decitabine (MESH:D000077209), bortezomib (MESH:D000069286), panobinostat (MESH:D000077767), cytosine (MESH:D003596), 5-methylcytosine (MESH:D044503), dexamethasone (MESH:D003907), Vorinostat (MESH:D000077337), alpha-ketoglutarate (MESH:D007656), 5-hydroxymethylcytosine (MESH:C011865), romidepsin (MESH:C087123), H3K4 (-), azacitidine (MESH:D001374), olutasidenib (MESH:C000710173), lysine (MESH:D008239), Tazemetostat (MESH:C000593333), ATP (MESH:D000255) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] - **Mutations:** R172K ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12916376/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12916376/full.md ## References 176 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916376/full.md --- Source: https://tomesphere.com/paper/PMC12916376