Skip to main content

Advertisement

SpringerLink
Log in

Transcriptome sequencing identifies novel EVX fusions involved in transcriptional activation of HOX family genes in pediatric immature T-cell acute lymphoblastic leukemia: two cases reports and a literature review

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Driver genomic alterations in pediatric immature T-cell acute lymphoblastic leukemia are not fully known. We report two cases of novel EVX fusions involved in the transcriptional activation of HOX family genes, ETV6::EVX2 and MSI2::EVX1/HOXA13, which activate HOXD and HOXA cluster genes transcription through enhancer hijacking. HOXA and HOXD were the only key transcription factors activated in these cases, which indicates their important roles in leukemogenesis. Our findings elucidate potential drivers for development of T-cell lymphoblastic leukemia, and are valuable for diagnosis and risk stratification of pediatric T-ALL in the era of precision medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data that support the findings of this study are openly available in [repository name] at [URL].

References

  1. Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147–56.

    Article  CAS  PubMed  Google Scholar 

  2. Belver L, Ferrando A. The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Nat Rev Cancer. 2016;16(8):494–507.

    Article  CAS  PubMed  Google Scholar 

  3. Graux C, Cools J, Michaux L, Vandenberghe P, Hagemeijer A. Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia. 2006;20(9):1496–510.

    Article  CAS  PubMed  Google Scholar 

  4. Soulier J, Clappier E, Cayuela JM, Regnault A, García-Peydró M, Dombret H, et al. HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). Blood. 2005;106(1):274–86.

    Article  CAS  PubMed  Google Scholar 

  5. Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49(8):1211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yang W, Cai J, Shen S, Gao J, Yu J, Hu S, et al. Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021;22(9):1322–32.

    Article  CAS  PubMed  Google Scholar 

  7. Cui L, Li ZG, Chai YH, Yu J, Gao J, Zhu XF, et al. Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: The first nation-wide prospective multicenter study in China. Am J Hematol. 2018;93(7):913–20.

    Article  PubMed  Google Scholar 

  8. Scott MP. A rational nomenclature for vertebrate homeobox (HOX) genes. Nucleic Acids Res. 1993;21(8):1687–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hnisz D, Weintraub AS, Day DS, Valton AL, Bak RO, Li CH, et al. Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science. 2016;351(6280):1454–8.

    Article  CAS  PubMed  Google Scholar 

  10. Beroukhim R, Zhang X, Meyerson M. Copy number alterations unmasked as enhancer hijackers. Nat Genet. 2016;49(1):5–6.

    Article  PubMed  Google Scholar 

  11. La Starza R, Pierini V, Pierini T, Nofrini V, Matteucci C, Arniani S, et al. Design of a comprehensive fluorescence in situ hybridization assay for genetic classification of T-cell acute lymphoblastic leukemia. J Mol Diagn. 2020;22(5):629–39.

    Article  PubMed  Google Scholar 

  12. Bond J, Marchand T, Touzart A, Cieslak A, Trinquand A, Sutton L, et al. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a group for research in adult acute lymphoblastic leukemia study. Haematologica. 2016;101(6):732–40.

    Article  CAS  PubMed  Google Scholar 

  13. Bergeron J, Clappier E, Cauwelier B, Dastugue N, Millien C, Delabesse E, et al. HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation. Leukemia. 2006;20(6):1184–7.

    Article  CAS  PubMed  Google Scholar 

  14. Liu Y, Li C, Shen S, Chen X, Szlachta K, Edmonson MN, et al. Discovery of regulatory noncoding variants in individual cancer genomes by using cis-X. Nat Genet. 2020;52(8):811–8.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481(7380):157–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Seki M, Kimura S, Isobe T, Yoshida K, Ueno H, Nakajima-Takagi Y, et al. Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia. Nat Genet. 2017;49(8):1274–81.

    Article  CAS  PubMed  Google Scholar 

  17. Parihar M, Gupta A, Remani AS, Bhattacharyya A, Mishra DK, Chandy M. Novel t(2;12)(q31;p13) in a case of pediatric T-cell acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2014;36(5):e313–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the following projects: National Natural Science Foundation of China (81970163 and 82170218 to SH), Jiangsu Project (BE2021654 to SH), Suzhou Project (GSWS2020039 to SH), the National Clinical Research Center for Hematological Disorders (2020ZKPB02 to SH), Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics (20dz2260900 to YL) and Innovative research team of high-level local universities in Shanghai (to YL).

Author information

Authors and Affiliations

  1. Department of Hematology, Jiangsu Children’s Hematology and Oncology Center, and the Children’s Hospital of Soochow University, Suzhou, 215025, China

    Xiao Zhang, Zhiheng Li, Jiajia Zheng, Xinran Chu, Peifang Xiao, Jun Lu & Shaoyan Hu

  2. Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Bowen Cui & Yu Liu

  3. Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, 215000, China

    Zheng Wang & Jiannong Cen

  4. Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Yu Liu

  5. Division of Pharmaceutical Sciences, Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas Place MS313, Memphis, TN, 38105, USA

    Yizhen Li

Authors
  1. Xiao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bowen Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yizhen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhiheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiajia Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xinran Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peifang Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jun Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jiannong Cen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shaoyan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XZ put all data together and drafted this manuscript. BC and YL analyzed the data. ZL interpreted the fusion genes’ action and JZ collected the clinical data. PX and JL made the treatment decision. XC, ZW and JC did RT-PCR for monitoring the MRD. YL and SH designed the study, reviewed the cases, and revised the manuscript.

Corresponding authors

Correspondence to Yu Liu or Shaoyan Hu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The studies involving human participants were reviewed and approved by the Ethics Committee of the Children’s Hospital of Soochow University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 13 KB)

Supplementary file2 (XLSX 10 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, X., Cui, B., Li, Y. et al. Transcriptome sequencing identifies novel EVX fusions involved in transcriptional activation of HOX family genes in pediatric immature T-cell acute lymphoblastic leukemia: two cases reports and a literature review. Int J Hematol 118, 508–513 (2023). https://doi.org/10.1007/s12185-023-03619-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-023-03619-6

Keywords

Search

Navigation