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Epigenetic alterations and advancement of lymphoma treatment

  • Review Article
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Annals of Hematology Aims and scope Submit manuscript

Abstract

Lymphomas, complex and heterogeneous malignant tumors, originate from the lymphopoietic system. These tumors are notorious for their high recurrence rates and resistance to treatment, which leads to poor prognoses. As ongoing research has shown, epigenetic modifications like DNA methylation, histone modifications, non-coding RNA regulation, and RNA modifications play crucial roles in lymphoma pathogenesis. Epigenetic modification–targeting drugs have exhibited therapeutic efficacy and tolerability in both monotherapy and combination lymphoma therapy. This review discusses pathogenic mechanisms and potential epigenetic therapeutic targets in common lymphomas, offering new avenues for lymphoma diagnosis and treatment. We also discuss the shortcomings of current lymphoma treatments, while suggesting potential areas for future research, in order to improve the prediction and prognosis of lymphoma.

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Data Availability

The datasets analysed during the current study are available to download from https://clinicaltrials.gov/.

Abbreviations

HL:

Hodgkin’s lymphoma

NHL:

Non-Hodgkin’s lymphoma

DLBCL:

Diffuse large B cell lymphoma

CAR-T:

Chimeric antigen receptor-modified T cell

CHOP:

Cyclophosphamide, doxorubicin, vincristine, and prednisone

CHOEP:

CHOP-like regimen

SCT:

Stem cell transplantation

DNMT:

DNA methyltransferases

5mC:

5-Methylcytosine

EBV:

Epstein-Barr virus

BL:

Burkitt lymphoma

UHRF1:

Ubiquitin-like, containing PHD and RING finger domains, 1

AZA:

5-Azacytidine

ROMI:

Romidepsin

CTAs:

Cancer testis antigens

PTCL:

Peripheral T cell lymphoma

TN:

Treatment-naïve

TFH:

T follicular helper cell

GC:

Germinal center

PRC2:

Polycomb repressor complex 2

HDAC:

Histone deacetylase

HDACi:

Histone deacetylase inhibitors

MCL:

Mantle cell lymphoma

ADCC:

Antibody-dependent cell-mediated cytotoxicity

MTCL:

Mature T cell lymphoma

CTCL:

Cutaneous T cell lymphoma

mTOR:

Mammalian target of rapamycin

AAK:

Aurora A kinase

ABK:

Aurora B kinase

AAKi:

Aurora A kinase inhibitors

JAKi:

Janus kinase inhibitors

C:

Completed

R:

Recruiting

ANR:

Active, not recruiting

DLT:

Dose-limiting toxicity

CRR:

Complete response rate

MTD:

Maximum tolerable dose

ORR:

Objective response rate

PRR:

Partial response rate

PFS:

Progression-free survival

PTCL:

Previously untreated peripheral T cell lymphoma

R/R:

Relapsed/refractory

ENKTCL:

Extranodal natural killer cell/T cell lymphoma

CTL:

Cutaneous T cell lymphoma

ATCL:

Angioimmunoblastic T cell lymphoma

TCL:

T cell lymphoma

MCL:

Mature cell lymphoma

AITL:

Angioimmunoblastic T cell lymphoma

CFDA:

The China Food and Drug Administration

IPI:

International prognostic index

CPET regimen:

Prednisone, etoposide, and thalidomide

PEL regimen:

Prednisone, etoposide, lenalidomide

PD-1:

Programmed death-1

PD-L1:

Anti-PD1-ligand 1

ICIs:

Immune checkpoint inhibitors

ncRNAs:

Non-coding RNAs

sncRNA:

Small non-coding RNAs

lncRNA:

Long-stranded non-coding RNAs

PTCL-NOS:

PTCL-not otherwise specified

BCL:

B cell lymphoma

m7G:

N7-methyluracil

m6A:

N6-methyladenosine

m5C:

5-Methylcytosine

METTL3:

Methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit

PEDF:

Pigment epithelium-derived factor

WTAP:

WT1-associated protein

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Acknowledgements

The work was supported by the Department of Hematology of Linyi People’s Hospital and Weifang Medical University, and I would like to show great gratitude to them all.

Funding

This study was supported by Shandong Provincial Postdoctoral Innovation Project (201903077) and Shandong Provincial Natural Science Foundation (ZR2018PH014).

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Authors and Affiliations

  1. Affiliated Hospital of Weifang Medical University, School of Clinical Medicine, Weifang Medical University, Weifang, China

    Shuhui Zhuang

  2. Department of Hematology, Linyi People’s Hospital, Shandong University, Linyi, 276000, Shandong, China

    Shuhui Zhuang, Zhuangzhuang Cui & Yuanyuan Zhang

  3. Spine Surgery, Linyi People’s Hospital, Shandong University, Linyi, 276000, Shandong, China

    Zhaobo Yang

  4. Department of Hematology, Shandong Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China

    Yuanyuan Zhang

  5. Department of Neurology, Central Laboratory and Key Laboratory of Neurophysiology, Linyi People’s Hospital, Shandong University, Linyi, 276000, China

    Fengyuan Che

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  1. Shuhui Zhuang
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All authors searched for the literature and wrote and edited the manuscript. All authors read and approved the final manuscript.

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Zhuang, S., Yang, Z., Cui, Z. et al. Epigenetic alterations and advancement of lymphoma treatment. Ann Hematol 103, 1435–1454 (2024). https://doi.org/10.1007/s00277-023-05395-z

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