# Exploiting cellular senescence in hematologic malignancies **Authors:** Peijie Jiang, Guancui Yang, Jiarun Li, Xiaolong Tian, Xueqing Yang, Shijie Yang, Jin Wei, Xi Zhang, Jinyi Liu PMC · DOI: 10.1016/j.tranon.2026.102729 · 2026-03-16 ## TL;DR This paper reviews how cellular senescence influences blood cancers and how targeting it could improve cancer treatments. ## Contribution The paper provides a comprehensive review of senescence's dual role in hematologic malignancies and potential therapeutic strategies. ## Key findings - Senescent cells exhibit features like SASP and metabolic changes that contribute to cancer progression. - Combining senolytics with chemotherapy improves treatment outcomes in blood cancers. - Cellular senescence can both promote and inhibit tumor growth, acting as a double-edged sword. ## Abstract •Characteristics of Senescent Cells: Morphological alterations, cell cycle arrest, DNA damage, SASP, SA-β-gal and lipofuscin, metabolic changes.•Therapeutic strategies targeting cellular senescence: inducing cellular senescence and eliminating senescent cells.•Combining current antitumor treatments and senolytics can eliminate senescent cells more effectively and improve treatment outcomes in hematologic malignancies. Characteristics of Senescent Cells: Morphological alterations, cell cycle arrest, DNA damage, SASP, SA-β-gal and lipofuscin, metabolic changes. Therapeutic strategies targeting cellular senescence: inducing cellular senescence and eliminating senescent cells. Combining current antitumor treatments and senolytics can eliminate senescent cells more effectively and improve treatment outcomes in hematologic malignancies. Cellular Senescence is characterized by stable cell cycle arrest and major changes in cell morphology and physiology. Accumulating evidence indicates that senescence-associated phenotypic alterations in blood cells drive the initiation and progression of hematologic malignancies. Therefore, we reviewed the phenotypes associated with cellular senescence and the regulatory mechanisms of cellular senescence in hematological malignancies. Notably, chemical induction of cellular senescence and selectively elimination of senescent cells can effectively inhibit tumor cell proliferation and enhance the efficacy of chemotherapy. This review also discusses the role of cellular senescence in the treatment of hematological malignancies, providing an in-depth understanding of the role of cellular senescence as a double-edged sword in cancer biology. Image, graphical abstract ## Full-text entities - **Genes:** PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, AURKA (aurora kinase A) [NCBI Gene 6790] {aka AIK, ARK1, AURA, BTAK, PPP1R47, STK15}, DICER1 (dicer 1, ribonuclease III) [NCBI Gene 23405] {aka DCR1, Dicer, Dicer1e, GLOW, HERNA, K12H4.8-LIKE}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, B3GAT1 (beta-1,3-glucuronyltransferase 1) [NCBI Gene 27087] {aka CD57, GLCATP, GLCUATP, HNK1, LEU7, NK-1}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CEBPB (CCAAT enhancer binding protein beta) [NCBI Gene 1051] {aka C/EBP-beta, IL6DBP, NF-IL6, TCF5}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, E2F3 (E2F transcription factor 3) [NCBI Gene 1871] {aka E2F-3}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Myc (Myc proto-oncogene, bHLH transcription factor) [NCBI Gene 17869] {aka Myc2, Niard, Nird, bHLHe39}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], ARRB1 (arrestin beta 1) [NCBI Gene 408] {aka ARB1, ARR1}, BCL2L1 (BCL2 like 1) [NCBI Gene 598] {aka BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52}, TP53BP1 (tumor protein p53 binding protein 1) [NCBI Gene 7158] {aka 53BP1, TDRD30, p202, p53BP1}, LPAR3 (lysophosphatidic acid receptor 3) [NCBI Gene 23566] {aka EDG7, Edg-7, GPCR, HOFNH30, LP-A3, LPA3}, IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021] {aka MCPH12, PLSTIRE}, Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}, RBL2 (RB transcriptional corepressor like 2) [NCBI Gene 5934] {aka BRUWAG, P130, Rb2}, GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, CBX5 (chromobox 5) [NCBI Gene 23468] {aka HEL25, HP1, HP1A, HP1alpha}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ZFP36L1 (ZFP36 like 1 zinc finger CCCH-type) [NCBI Gene 677] {aka BRF1, Berg36, ERF-1, ERF1, RNF162B, TIS11B}, BCL2L2 (BCL2 like 2) [NCBI Gene 599] {aka BCL-W, BCL2-L-2, BCLW, PPP1R51}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, ATG7 (autophagy related 7) [NCBI Gene 10533] {aka APG7-LIKE, APG7L, GSA7, SCAR31}, EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, MYOM2 (myomesin 2) [NCBI Gene 9172] {aka TTNAP}, Cdkn2a (cyclin dependent kinase inhibitor 2A) [NCBI Gene 12578] {aka ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1}, CD5 (CD5 molecule) [NCBI Gene 921] {aka LEU1, T1}, SUV39H1 (SUV39H1 histone lysine methyltransferase) [NCBI Gene 6839] {aka H3-K9-HMTase 1, KMT1A, MG44, SUV39H}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, MCL1 (MCL1 apoptosis regulator, BCL2 family member) [NCBI Gene 4170] {aka BCL2L3, EAT, MCL1-ES, MCL1L, MCL1S, Mcl-1}, LPAR1 (lysophosphatidic acid receptor 1) [NCBI Gene 1902] {aka EDG2, Gpcr26, LPA1, Mrec1.3, VZG1, edg-2}, LPA (lipoprotein(a)) [NCBI Gene 4018] {aka AK38, APOA, LP}, DDIT4 (DNA damage inducible transcript 4) [NCBI Gene 54541] {aka Dig2, REDD-1, REDD1}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, CDK2 (cyclin dependent kinase 2) [NCBI Gene 1017] {aka CDKN2, p33(CDK2)}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163} - **Diseases:** Lymphoid malignancies (MESH:D008223), Lymphoid leukemia (MESH:D007945), NHL (MESH:D008228), breast cancer (MESH:D001943), renal failure (MESH:D051437), genetic abnormalities (MESH:D030342), hematologic malignancies (MESH:D019337), MDS (MESH:D009190), HL (MESH:D006689), hypercalcemia (MESH:D006934), CML (MESH:D015464), inflammatory (MESH:D007249), ALL (MESH:D054198), precancerous (MESH:D011230), melanoma (MESH:D008545), T-cell malignancies (MESH:D016399), SMM (MESH:D000075122), B-CLL (MESH:D015451), SASP (MESH:D008579), cancer (MESH:D009369), anemia (MESH:D000740), dysplasia (MESH:D015792), non-small cell lung cancer (MESH:D002289), cytopenia (MESH:D006402), gastrointestinal AEs (MESH:D005767), plasma cell disorders (MESH:D007952), Mitochondrial dysfunction (MESH:D028361), aplastic anemia (MESH:D000741), GI AEs (MESH:D006470), MM (MESH:D009101), bone lesions (MESH:D001847), tumorigenesis (MESH:D063646), OIS (MESH:D000074723), obese (MESH:D009765), leukemia (MESH:D007938), ML (MESH:D007951), AML (MESH:D015470) - **Chemicals:** vitamin D (MESH:D014807), ATP (MESH:D000255), AKI603 (MESH:C000597114), nutlin-3a (MESH:C482205), ABT-263 (MESH:C528561), flavonoid (MESH:D005419), acetyl-CoA (MESH:D000105), SD-208 (MESH:C511004), pyruvate (MESH:D019289), venetoclax (MESH:C579720), idasanutlin (MESH:C586849), quercetin (MESH:D011794), dabrafenib (MESH:C561627), VEM (MESH:D000077484), ROS (MESH:D017382), palbociclib (MESH:C500026), 5-aza-2'-deoxycytidine (MESH:D000077209), Hesperetin (MESH:C013015), abemaciclib (MESH:C000590451), dasatinib (MESH:D000069439), MLN8237 (MESH:C550258), RG7112 (MESH:C579783), GSH (MESH:D005978), Bortezomib (MESH:D000069286), 4-Methylumbelliferone (MESH:D006923), SA- (MESH:D000077145), daunorubicin (MESH:D003630), vincristine (MESH:D014750), Lipofuscin (MESH:D008062), trametinib (MESH:C560077), WM-1119 (MESH:C000630881), lipid (MESH:D008055), Doxorubicin (MESH:D004317), ADP (MESH:D000244), hyaluronic acid (MESH:D006820), lenalidomide (MESH:D000077269), AMG232 (MESH:C000726938), 4Mu (-), Curcumin (MESH:D003474), WM-8014 (MESH:C000630872), imatinib (MESH:D000068877), rapamycin (MESH:D020123), TCA (MESH:D014233), fatty acid (MESH:D005227), AMP (MESH:D000249), oxygen (MESH:D010100), indoxyl sulfate (MESH:D007200) - **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** BrafV600E, T315I - **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985) ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13011199/full.md --- Source: https://tomesphere.com/paper/PMC13011199