Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

CHRONIC LYMPHOCYTIC LEUKEMIA

High incidence of MYD88 and KMT2D mutations in Chinese with chronic lymphocytic leukemia

Leukemia volume 35, pages 2412–2415 (2021)Cite this article

Subjects

Chronic lymphocytic leukemia (CLL), the most common leukemia in persons of European descent, has a marked lower age-adjusted incidence rate in East Asians [1]. Asians with CLL are younger and have some distinct phenotype and genotype features. Chinese with CLL have a >60–70 percent frequency of mutated IGHV, involvement of IGHV3-7, IGHV3-74, IGHV4-39 and stereotype subset #8 of the specific complementary-determining region stereotype compared with Europeans [2, 3]. Several large-scale sequencing studies of persons with CLL of predominately Europeans descent (Western CLL) identified recurrent somatic driver mutations [4,5,6] but there are few such studies in Asians [4,5,6,7,8]. A recent study of mutations in TP53, SF3B1, NOTCH1, MYD88 and BIRC3 in Chinese with CLL using Sanger sequencing reported a 10% frequency of MYD88 mutations compared with 2–4% in Europeans [4, 5, 7]. This was validated in other cohorts from Hong Kong and Singapore [8]. Both studies failed to determine statistically significant genetic differences between Western and Asian CLL due to the low sensitivity of Sanger sequencing and limited numbers of genes examined [7, 8].

To gain a better understanding of the mutation topography of Asians with CLL, we studied mutations in 91 genes in 126 Chinese patients with CLL using next generation sequencing and validated the top 20 recurrent mutated genes in another 212 patients. The baseline characteristics of 303 untreated and 35 relapsed patients studied were summarized in Table S1.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Landscape of recurrent mutated genes and clinical associations.
Fig. 2: KMT2D mutations and their functional impacts on CLL cells.

References

  1. Gale RP, Cozen W, Goodman MT, Wang FF, Bernstein L. Decreased chronic lymphocytic leukemia incidence in Asians in Los Angeles County. Leuk Res. 2000;24:665–9.

    Article  CAS  Google Scholar 

  2. Marinelli M, Ilari C, Xia Y, Del Giudice I, Cafforio L, Della Starza I, et al. Immunoglobulin gene rearrangements in Chinese and Italian patients with chronic lymphocytic leukemia. Oncotarget. 2016;7:20520–31.

    Article  Google Scholar 

  3. Wu SJ, Lin CT, Agathangelidis A, Lin LI, Kuo YY, Tien HF, et al. Distinct molecular genetics of chronic lymphocytic leukemia in Taiwan: clinical and pathogenetic implications. Haematologica. 2017;102:1085–90.

    Article  CAS  Google Scholar 

  4. Landau DA, Tausch E, Taylor-Weiner AN, Stewart C, Reiter JG, Bahlo J, et al. Mutations driving CLL and their evolution in progression and relapse. Nature. 2015;526:525–30.

    Article  CAS  Google Scholar 

  5. Puente XS, Bea S, Valdes-Mas R, Villamor N, Gutierrez-Abril J, Martin-Subero JI, et al. Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature. 2015;526:519–24.

    Article  CAS  Google Scholar 

  6. Nadeu F, Clot G, Delgado J, Martin-Garcia D, Baumann T, Salaverria I, et al. Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia. Leukemia. 2018;32:645–53.

    Article  CAS  Google Scholar 

  7. Xia Y, Fan L, Wang L, Gale RP, Wang M, Tian T, et al. Frequencies of SF3B1, NOTCH1, MYD88, BIRC3 and IGHV mutations and TP53 disruptions in Chinese with chronic lymphocytic leukemia: disparities with Europeans. Oncotarget. 2015;6:5426–34.

    Article  Google Scholar 

  8. Chan TS, Lee YS, Del Giudice I, Marinelli M, Ilari C, Cafforio L, et al. Clinicopathological features and outcome of chronic lymphocytic leukaemia in Chinese patients. Oncotarget. 2017;8:25455–68.

    Article  Google Scholar 

  9. Froimchuk E, Jang Y, Ge K. Histone H3 lysine 4 methyltransferase KMT2D. Gene. 2017;627:337–42.

    Article  CAS  Google Scholar 

  10. Green MR, Kihira S, Liu CL, Nair RV, Salari R, Gentles AJ, et al. Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation. Proc Natl Acad Sci USA. 2015;112:E1116–25.

    Article  CAS  Google Scholar 

  11. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476:298–303.

    Article  CAS  Google Scholar 

  12. Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011;43:830–7.

    Article  CAS  Google Scholar 

  13. Agathangelidis A, Darzentas N, Hadzidimitriou A, Brochet X, Murray F, Yan XJ, et al. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood. 2012;119:4467–75.

    Article  CAS  Google Scholar 

  14. Rossi D, Spina V, Bomben R, Rasi S, Dal-Bo M, Bruscaggin A, et al. Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia. Blood. 2013;121:4902–5.

    Article  CAS  Google Scholar 

  15. Gounari M, Ntoufa S, Apollonio B, Papakonstantinou N, Ponzoni M, Chu CC, et al. Excessive antigen reactivity may underlie the clinical aggressiveness of chronic lymphocytic leukemia stereotyped subset #8. Blood. 2015;125:3580–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Supported by grants from the National Nature Science Foundation of China (81970187, 81570181, 81890990, 81861148029  and 81630007), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-2-009 and 2017-I2M-3-018), Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018RC320012, 2018PT31006), Tianjin Science and Technology Supporting Program (17JCYBJC27900) and the National Science and Technology Major Project (2017ZX09304024), the Ministry of Science and Technology of China (2020YFE0203000). RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. LW acknowledges support from City of Hope. We thank for Profs. Kanti Rai (Northwell University), Neil Kay (Mayo Clinic), Federico Caligaris-Cappio (Italian Association for Cancer Research) and Robin Foà (La Sapienza University of Rome) for kindly reviewing the manuscript. Dr. Sarah Wilkinson (City of Hope) helped for editing the manuscript.

Author information

Author notes

  1. These authors contributed equally: Shuhua Yi, Yuting Yan, Meiling Jin, Lili Wang, Lugui Qiu

Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Blood Diseases Hospital & Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Shuhua Yi, Yuting Yan, Wenjie Xiong, Zhen Yu, Ying Yu, Rui Cui, Jun Wang, Yi Wang, Yani Lin, Yujiao Jia, Donglei Zhang, Tingyu Wang, Rui Lv, Wei Liu, Weiwei Sui, Wenyang Huang, Mingwei Fu, Yan Xu, Shuhui Deng, Gang An, Dehui Zou, Zengjun Li, Jun Shi, Zhijian Xiao, Jianxiang Wang, Tao Cheng & Lugui Qiu

  2. Department of Systems Biology, Beckman Research Institute, City of Hope National Comprehensive Cancer Center, Monrovia, CA, 91016, USA

    Meiling Jin & Lili Wang

  3. Department of Hematology, Tianjin First Center Hospital, Tianjin, 300192, China

    Rui Cui

  4. Centre for Haematology Research, Department of Immunology and Inflammation, Imperial College London, London, UK

    Robert Peter Gale

Authors
  1. Shuhua Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuting Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meiling Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenjie Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhen Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rui Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yani Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yujiao Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Donglei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tingyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Rui Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Wei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Weiwei Sui
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Wenyang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Mingwei Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Shuhui Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Gang An
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Dehui Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Zengjun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Jun Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Zhijian Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Jianxiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Tao Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Robert Peter Gale
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Lili Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Lugui Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lili Wang or Lugui Qiu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yi, S., Yan, Y., Jin, M. et al. High incidence of MYD88 and KMT2D mutations in Chinese with chronic lymphocytic leukemia. Leukemia 35, 2412–2415 (2021). https://doi.org/10.1038/s41375-021-01124-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-021-01124-5

This article is cited by

Search

Advanced search

Quick links