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:

Lymphoma

Treatment and outcome of IG-MYC+ neoplasms with precursor B-cell phenotype in childhood and adolescence

Leukemia volume 34, pages 942–946 (2020)Cite this article

Subjects

The translocation of the MYC gene on chromosome 8q24 to one of the immunoglobulin loci, leading to overexpression of MYC and cell proliferation is considered the hallmark of Burkitt leukemia/lymphoma (BL). It also occurs in a plethora of other B-cell Non-Hodgkin lymphoma (NHL), including plasmablastic lymphoma, diffuse large B-cell lymphoma, multiple myeloma, and rarely in precursor B-cell leukemia/lymphoma (pB-acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL)/LBL) [1,2,3,4,5,6,7,8,9,10,11,12]. Although the “WHO Classification of Haematopoetic and Lymphoid Tissue [13] acknowledges rare cases of BL exhibiting a precursor B-cell phenotype (termed herein preBLL in the following), recent evidence suggests that these neoplasms genetically and epigenetically resemble pB-ALL/LBL rather than BL [14]. Information on the clinical implications of the pathogenesis is scarce and so far, only few cases of preBLL in childhood and adolescence have been reported [1,2,3,4,5,6,7,8,9,10,11,12]. Treatment paradigms for pB-ALL/LBL and BL differ substantially so that these molecular findings ignite the ongoing debate on the optimal management of patients with preBLL. Whereas protocols for BL consist of short, highly intensive pulsed chemotherapeutic regimen complemented by rituximab, protocols for pB-ALL/LBL are characterized by more continuous treatment regimen extended by a maintenance therapy of low intensity. In light of the rarity of preBLL and the paucity of published reports with heterogenous treatment approaches, the choice of the appropriate treatment regimen for patients with preBLL currently is almost impossible. The diagnosis of preBLL often is hampered by ambiguities and delays further complicating the clinical management of patients with overlapping features between BL and pB-ALL/LBL.

To elucidate the outcome of patients treated according to NHL-Berlin–Frankfurt–Muenster (BFM) protocols for mature B-cell NHL and further describe the frequency, clinical, cytomorphologic, immunophenotypic, and genetic characteristics of preBLL, we report on the largest cohort of children and adolescents with central review of the diagnosis.

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

References

  1. Meznarich J, Miles R, Paxton CN, Afify Z. Pediatric B-Cell lymphoma with lymphoblastic morphology, TdT expression, MYC rearrangement, and features overlapping with Burkitt lymphoma. Pediatr Blood Cancer. 2016;63:938–40.

    Article  Google Scholar 

  2. Navid F, Mosijczuk AD, Head DR, Borowitz MJ, Carroll AJ, Brandt JM, et al. Acute lymphoblastic leukemia with the (8;14)(q24; q32) translocation and FAB L3 morphology associated with a B-precursor immunophenotype: the Pediatric Oncology Group experience. Leukemia. 1999;13:135–41.

    Article  CAS  Google Scholar 

  3. Kaneko Y, Rowley JD, Check I, Variakojis D, Moohr JW. The 14q+ chromosome in pre-B-ALL. Blood. 1980;56:782–5.

    Article  CAS  Google Scholar 

  4. Wodzinski MA, Watmore AE, Lilleyman JS, Potter AM. Chromosomes in childhood acute lymphoblastic leukaemia: karyotypic patterns in disease subtypes. J Clin Pathol. 1991;44:48–51.

    Article  CAS  Google Scholar 

  5. Loh ML, Samson Y, Motte E, Moreau LA, Dalton V, Waters S, et al. Translocation (2;8)(p12; q24) associated with a cryptic t(12;21)(p13;q22) TEL/AML1 gene rearrangement in a child with acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2000;122:79–82.

    Article  CAS  Google Scholar 

  6. Reid MM, Drewery C, Windebank KP. Surface immunoglobulin-negative acute lymphoblastic leukaemia with predominant L1 morphology, occasional L3 cells and t(8;22). Br J Haematol. 2003;122:693.

    Article  Google Scholar 

  7. Gupta AA, Grant R, Shago M, Abdelhaleem M. Occurrence of t(8;22)(q24.1; q11.2) involving the MYC locus in a case of pediatric acute lymphoblastic leukemia with a precursor B cell immunophenotype. J Pediatr Hematol Oncol. 2004;26:532–4.

    Article  Google Scholar 

  8. Hassan R, Felisbino F, Stefanoff CG, Pires V, Klumb CE, Dobbin J, et al. Burkitt lymphoma/leukaemia transformed from a precursor B cell: clinical and molecular aspects. Eur J Haematol. 2008;80:265–70.

    Article  Google Scholar 

  9. Meeker ND, Cherry AM, Bangs CD, Frazer JK. A pediatric B lineage leukemia with coincident MYC and MLL translocations. J Pediatr Hematol Oncol. 2011;33:158–60.

    Article  Google Scholar 

  10. Roug AS, Wendtland P, Bendix K, Kjeldsen E. Supernumerary isochromosome 1, idic(1)(p12), leading to tetrasomy 1q in Burkitt lymphoma. Cytogenet Genome Res. 2014;142:7–13.

    Article  CAS  Google Scholar 

  11. Sato Y, Kurosawa H, Fukushima K, Okuya M, Arisaka O. Burkitt-type acute lymphoblastic leukemia with precursor B-cell immunophenotype and partial tetrasomy of 1q: a case report. Med (Baltim). 2016;95:e2904.

    Article  Google Scholar 

  12. Bessenyei B, Ujfalusi A, Balogh E, Olah E, Szegedi I, Kiss C. Jumping translocation of chromosome 1q associated with good clinical outcome in a case of Burkitt leukemia. Cancer Genet. 2011;204:207–10.

    Article  CAS  Google Scholar 

  13. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumors of hematopoietic and lymphoid tissues. 4th ed.. Lyon: IARC Press; 2008.

  14. Wagener R, Lopez C, Kleinheinz K, Bausinger J, Aukema SM, Nagel I, et al. IG-MYC (+) neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas. Blood. 2018;132:2280–5.

    Article  CAS  Google Scholar 

  15. Varano G, Raffel S, Sormani M, Zanardi F, Lonardi S, Zasada C, et al. The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3beta inhibition. Nature. 2017;546:302–6.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Ulrike Meyer, Claudia Sopalla, Nora Muehlegger (data management), and Gabi Buck (cytomorphology) for their expert work. We also thank the patients, parents, and guardians as well as physicians, nurses, and data managers in the participating centers of the NHL‐BFM group who cared for the children and adolescents and supplied data. We thank the Deutsche Kinderkrebsstiftung for support of the NHL-BFM Registry 2012 (DKS 2014.11 A/B). WK and RS are supported by the Kinderkrebsinitiative Buchholz, Holm‐Seppensen (KKI). The Austrian NHL‐BFM Study Group was supported by the St. Anna Kinderkrebsforschung (Children’s Cancer Research Institute).

Author information

Authors and Affiliations

  1. Pediatric Hematology and Oncology, University Hospital Muenster, Muenster, Germany

    Heidi Herbrueggen, Stephanie Mueller, Laura Arias Padilla & Birgit Burkhardt

  2. General Pediatrics, University Hospital Muenster, Muenster, Germany

    Jonas Rohde

  3. Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Anja Moericke

  4. Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Vienna, Austria

    Andishe Attarbaschi

  5. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

    Martin Zimmermann

  6. Department of Oncology, Hematology, and Palliative Care, Helios Clinic Bad Saarow, Bad Saarow, Germany

    Richard Ratei

  7. Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Monika Brueggemann

  8. Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany

    Reiner Siebert

  9. Department of Human Genetics, Hannover Medical School, Hannover, Germany

    Gudrun Goehring & Brigitte Schlegelberger

  10. Department of Pathology, University of Giessen, Giessen, Germany

    Jutta Bradtke

  11. Department of Pathology, Hematopathology Section, University Hospital Schleswig-Holstein, Kiel, Germany

    Wolfram Klapper

  12. Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Willi Woessmann

Authors
  1. Heidi Herbrueggen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephanie Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonas Rohde
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laura Arias Padilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anja Moericke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andishe Attarbaschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martin Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Richard Ratei
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Monika Brueggemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Reiner Siebert
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gudrun Goehring
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Brigitte Schlegelberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jutta Bradtke
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Wolfram Klapper
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Willi Woessmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Birgit Burkhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Birgit Burkhardt.

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

Herbrueggen, H., Mueller, S., Rohde, J. et al. Treatment and outcome of IG-MYC+ neoplasms with precursor B-cell phenotype in childhood and adolescence. Leukemia 34, 942–946 (2020). https://doi.org/10.1038/s41375-019-0606-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-019-0606-6

Search

Advanced search

Quick links