Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma

Emma Kroeze, Ingram Iaccarino, Michelle M. Kleisman, Mayukh Mondal, Thomas Beder, Mouhamad Khouja, Marc P. Höppner, Marijn A. Scheijde-Vermeulen, Lennart A. Kester, Monika Brüggemann, Claudia D. Baldus, Gunnar Cario, Reno S. Bladergroen, Nathalie Garnier, Andishe Attarbaschi, Jaime Verdu-Amorós, Rosemary Sutton, Elizabeth Macintyre, Kenneth Scholten, Laura Arias PadillaBirgit Burkhardt, Auke Beishuizen, Monique L. den Boer, Roland P. Kuiper, Jan L.C. Loeffen, Judith M. Boer, Wolfram Klapper*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


Pediatric B-cell precursor (BCP) lymphoblastic malignancies are neoplasms with manifestation either in the bone marrow or blood (BCP acute lymphoblastic leukemia [BCP-ALL]) or are less common in extramedullary tissue (BCP lymphoblastic lymphoma [BCP-LBL]). Although both presentations are similar in morphology and immunophenotype, molecular studies have been virtually restricted to BCP-ALL so far. The lack of molecular studies on BCP-LBL is due to its rarity and restriction on small, mostly formalin-fixed paraffin-embedded (FFPE) tissues. Here, to our knowledge, we present the first comprehensive mutational and transcriptional analysis of what we consider the largest BCP-LBL cohort described to date (n = 97). Whole-exome sequencing indicated a mutational spectrum of BCP-LBL, strikingly similar to that found in BCP-ALL. However, epigenetic modifiers were more frequently mutated in BCP-LBL, whereas BCP-ALL was more frequently affected by mutation in genes involved in B-cell development. Integrating copy number alterations, somatic mutations, and gene expression by RNA sequencing revealed that virtually all molecular subtypes originally defined in BCP-ALL are present in BCP-LBL, with only 7% of lymphomas that were not assigned to a subtype. Similar to BCP-ALL, the most frequent subtypes of BCP-LBL were high hyperdiploidy and ETV6::RUNX1. Tyrosine kinase/cytokine receptor rearrangements were detected in 7% of BCP-LBL. These results indicate that genetic subtypes can be identified in BCP-LBL using next-generation sequencing, even in FFPE tissue, and may be relevant to guide treatment.

Original languageEnglish
Pages (from-to)74-83
Number of pages10
Issue number1
Publication statusPublished - 8 Apr 2024

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© 2024 American Society of Hematology


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