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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Pathology and Forensic Medicine

Acute lymphoblastic leukaemia

B-cell lineage

BCL6

immunohistochemistry

mRNA expression

paediatric

Medicinsk genetik

Medical Genetics

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