Expression of BCL6 in paediatric B-cell acute lymphoblastic leukaemia and association with prognosis

Artturi Mäkinen, Atte Nikkilä, Juha Mehtonen, Susanna Teppo, Laura Oksa, Jessica Nordlund, Samuli Rounioja, Virva Pohjolainen, Saara Laukkanen, Merja Heinäniemi, Timo Paavonen, Olli Lohi

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

B-cell lineage acute lymphoblastic leukaemia (B-ALL) is the most common paediatric malignancy. Transcription factor B-cell lymphoma 6 (BCL6) is essential to germinal centre formation and antibody affinity maturation and plays a major role in mature B-cell malignancies. More recently, it was shown to act as a critical downstream regulator in pre-BCR+ B-ALL. We investigated the expression of the BCL6 protein in a population-based cohort of paediatric B-ALL cases and detected moderate to strong positivity through immunohistochemistry in 7% of cases (8/117); however, only two of eight BCL6 cases (25%) co-expressed the ZAP70 protein. In light of these data, the subtype with active pre-BCR signalling constitutes a rare entity in paediatric B-ALL. In three independent larger cohorts with gene expression data, high BCL6 mRNA levels were associated with the TCF3-PBX1, Ph-like, NUTM1, MEF2D and PAX5-alt subgroups and the ‘metagene’ signature for pre-BCR-associated genes. However, higher-than-median BCL6 mRNA level alone was associated with favourable event free survival in the Nordic paediatric cohort, indicating that using BCL6 as a diagnostic marker requires careful design, and evaluation of protein level is needed alongside the genetic or transcriptomic data.

Original languageEnglish
JournalPATHOLOGY
DOIs
Publication statusE-pub ahead of print - 26 May 2021
Publication typeA1 Journal article-refereed

Keywords

  • Acute lymphoblastic leukaemia
  • B-cell lineage
  • BCL6
  • immunohistochemistry
  • mRNA expression
  • paediatric

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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