Altered pathways and targeted therapy in double hit lymphoma

doi:10.1186/s13045-022-01249-9

Review

. 2022 Mar 18;15(1):26.

doi: 10.1186/s13045-022-01249-9.

Altered pathways and targeted therapy in double hit lymphoma

Yuxin Zhuang^#^{1

2}, Jinxin Che^#^{2

3}, Meijuan Wu^#⁴, Yu Guo³, Yongjin Xu¹, Xiaowu Dong^{5

6

7}, Haiyan Yang⁸

Affiliations

¹ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, People's Republic of China.
² Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
³ Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, People's Republic of China.
⁴ Department of Pathology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, People's Republic of China.
⁵ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China. dongxw@zju.edu.cn.
⁶ Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, People's Republic of China. dongxw@zju.edu.cn.
⁷ Cancer Center, Zhejiang University, Hangzhou, People's Republic of China. dongxw@zju.edu.cn.
⁸ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, People's Republic of China. yanghy@zjcc.org.cn.

^# Contributed equally.

PMID: 35303910
PMCID: PMC8932183
DOI: 10.1186/s13045-022-01249-9

Review

Altered pathways and targeted therapy in double hit lymphoma

Yuxin Zhuang et al. J Hematol Oncol. 2022.

. 2022 Mar 18;15(1):26.

doi: 10.1186/s13045-022-01249-9.

Authors

Yuxin Zhuang^#^{1

2}, Jinxin Che^#^{2

3}, Meijuan Wu^#⁴, Yu Guo³, Yongjin Xu¹, Xiaowu Dong^{5

6

7}, Haiyan Yang⁸

Affiliations

¹ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, People's Republic of China.
² Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
³ Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, People's Republic of China.
⁴ Department of Pathology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, People's Republic of China.
⁵ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China. dongxw@zju.edu.cn.
⁶ Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, People's Republic of China. dongxw@zju.edu.cn.
⁷ Cancer Center, Zhejiang University, Hangzhou, People's Republic of China. dongxw@zju.edu.cn.
⁸ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, People's Republic of China. yanghy@zjcc.org.cn.

^# Contributed equally.

PMID: 35303910
PMCID: PMC8932183
DOI: 10.1186/s13045-022-01249-9

Abstract

High-grade B-cell lymphoma with translocations involving MYC and BCL2 or BCL6, usually referred to as double hit lymphoma (DHL), is an aggressive hematological malignance with distinct genetic features and poor clinical prognosis. Current standard chemoimmunotherapy fails to confer satisfying outcomes and few targeted therapeutics are available for the treatment against DHL. Recently, the delineating of the genetic landscape in tumors has provided insight into both biology and targeted therapies. Therefore, it is essential to understand the altered signaling pathways of DHL to develop treatment strategies with better clinical benefits. Herein, we summarized the genetic alterations in the two DHL subtypes (DHL-BCL2 and DHL-BCL6). We further elucidate their implications on cellular processes, including anti-apoptosis, epigenetic regulations, B-cell receptor signaling, and immune escape. Ongoing and potential therapeutic strategies and targeted drugs steered by these alterations were reviewed accordingly. Based on these findings, we also discuss the therapeutic vulnerabilities that coincide with these genetic changes. We believe that the understanding of the DHL studies will provide insight into this disease and capacitate the finding of more effective treatment strategies.

Keywords: Chemotherapy; Diffuse large B-cell lymphoma; Double hit lymphoma; Genetic alterations; Targeted therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interests.

Figures

**Fig. 1**
Genetic and pathways alterations involved in DHL-BCL2

**Fig. 2**
Genetic and pathways alterations involved in DHL-BCL6. Note: *genes associated with the ubiquitin–proteasome system; #: the consequence of *UBE2A* mutation is not fully illustrated, might be functionally damaging [142]

**Fig. 3**
Structures of targeted agents in DHL-BCL2

**Fig. 4**
Structures of targeted agents in DHL-BCL6

See this image and copyright information in PMC

Cited by

Primary cardiac large B cell lymphoma.
Arun Kumar S, Mishra R, Malempati SC, Bindal P. Arun Kumar S, et al. BMJ Case Rep. 2023 Dec 26;16(12):e256167. doi: 10.1136/bcr-2023-256167. BMJ Case Rep. 2023. PMID: 38151268
TBL1X: At the crossroads of transcriptional and posttranscriptional regulation.
Pray BA, Youssef Y, Alinari L. Pray BA, et al. Exp Hematol. 2022 Dec;116:18-25. doi: 10.1016/j.exphem.2022.09.006. Epub 2022 Oct 4. Exp Hematol. 2022. PMID: 36206873 Free PMC article. Review.
Double‑hit primary lymphoma (MYC and BCL2) in the bilateral ovary: A case report.
Zhang Y, Wang W, Chen T. Zhang Y, et al. Oncol Lett. 2023 Feb 22;25(4):141. doi: 10.3892/ol.2023.13727. eCollection 2023 Apr. Oncol Lett. 2023. PMID: 36909376 Free PMC article.
Validation of MYC and BCL6 rapid break apart digital fluorescence in situ hybridization assays for clinical use.
Liew M, Rowe L, Moore K, Aston E, O'Brien K, Longhurst M, Kenney J, Priest M, Zhou W, Wilcock D, Rets A, Miles R. Liew M, et al. Int J Clin Exp Pathol. 2023 Apr 15;16(4):76-85. eCollection 2023. Int J Clin Exp Pathol. 2023. PMID: 37168512 Free PMC article.
Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B-cell lymphoma.
Li MW, Huang FX, Xie ZC, Hong HY, Xu QY, Peng ZG. Li MW, et al. Cancer Med. 2023 Feb;12(3):3812-3829. doi: 10.1002/cam4.5115. Epub 2022 Aug 16. Cancer Med. 2023. PMID: 36812125 Free PMC article.

See all "Cited by" articles

References

1. Siegel RL, Miller KD, Jemal A. Cancer statistics 2020. CA Cancer J Clin. 2020;70(1):7–30. doi: 10.3322/caac.21590. - DOI - PubMed
1. Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, Scott DW, Tan KL, Steidl C, Sehn LH, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(28):3452–3459. - PMC - PubMed
1. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390. - PMC - PubMed
1. Swerdlow SH. Diagnosis of 'double hit' diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma: when and how, FISH versus IHC. Hematol Am Soc Hematol Educ Program. 2014;2014(1):90–99. - PubMed
1. Sesques P, Johnson NA. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood. 2017;129(3):280–288. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources

[1] Siegel RL, Miller KD, Jemal A. Cancer statistics 2020. CA Cancer J Clin. 2020;70(1):7–30. doi: 10.3322/caac.21590. - DOI - PubMed

[2] Siegel RL, Miller KD, Jemal A. Cancer statistics 2020. CA Cancer J Clin. 2020;70(1):7–30. doi: 10.3322/caac.21590. - DOI - PubMed

[3] Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, Scott DW, Tan KL, Steidl C, Sehn LH, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(28):3452–3459. - PMC - PubMed

[4] Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, Scott DW, Tan KL, Steidl C, Sehn LH, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(28):3452–3459. - PMC - PubMed

[5] Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390. - PMC - PubMed

[6] Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390. - PMC - PubMed

[7] Swerdlow SH. Diagnosis of 'double hit' diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma: when and how, FISH versus IHC. Hematol Am Soc Hematol Educ Program. 2014;2014(1):90–99. - PubMed

[8] Swerdlow SH. Diagnosis of 'double hit' diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma: when and how, FISH versus IHC. Hematol Am Soc Hematol Educ Program. 2014;2014(1):90–99. - PubMed

[9] Sesques P, Johnson NA. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood. 2017;129(3):280–288. - PubMed

[10] Sesques P, Johnson NA. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood. 2017;129(3):280–288. - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Altered pathways and targeted therapy in double hit lymphoma

Affiliations

Altered pathways and targeted therapy in double hit lymphoma

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources