What is BCL6?

Reviewed by Pathologists
December 29, 2025

BCL6 is a gene that provides instructions for making the BCL6 protein, which acts as a transcription factor. A transcription factor is a protein that controls which genes inside a cell are turned on or off.

BCL6 is considered a biomarker. A biomarker is a measurable feature in a tumour, such as a gene change or protein expression, that helps pathologists diagnose cancer, classify its type, and estimate how it may behave.

What is the function of BCL6 in normal cells?

In normal tissue, BCL6 plays an essential role in the immune system. It is mainly active in germinal center B cells, which are specialized immune cells found in lymph nodes and other lymphoid tissues. These cells normally undergo controlled DNA changes to help the body produce effective antibodies.

BCL6 helps protect these cells from dying during this process by temporarily blocking cell-death signals triggered by DNA damage. It also plays a role in the development of follicular helper T cells, which help guide immune responses.

What types of cancer are associated with BCL6?

Abnormal BCL6 expression or gene changes are most commonly associated with lymphomas, including:

• Diffuse large B-cell lymphoma (DLBCL).

• Follicular lymphoma.

• High-grade B-cell lymphomas, including so-called “double-hit” and “triple-hit” lymphomas.

• Burkitt lymphoma.

• Certain T-cell lymphomas, particularly those derived from follicular helper T cells, such as angioimmunoblastic T-cell lymphoma.

BCL6 expression may also be seen in a small number of non-lymphoid tumours, but its main clinical importance is in blood and lymphatic cancers.

How does BCL6 cause cancer?

Cancer can develop when cells avoid normal safeguards that limit growth and survival.

When BCL6 is abnormally active, it can suppress important protective genes that normally stop damaged cells from surviving. This allows cells with genetic abnormalities to continue dividing rather than undergo programmed cell death.

In some aggressive lymphomas, BCL6 is involved in gene rearrangements, often in combination with rearrangements of other genes, such as MYC or BCL2. These combined changes define particularly aggressive cancers known as double-hit or triple-hit lymphomas.

Why do pathologists test for BCL6?

Pathologists test for BCL6 because it provides important diagnostic, classification, and prognostic information, especially in lymphomas.

BCL6 testing can help:

• Identify germinal center–derived lymphomas.

• Distinguish follicular lymphoma from benign reactive conditions.

• Classify diffuse large B-cell lymphoma into biologically meaningful subtypes.

• Identify aggressive lymphomas when combined with MYC and BCL2 testing.

These distinctions can affect prognosis and influence treatment planning.

How do pathologists test for BCL6?

BCL6 testing is usually performed on tumour tissue from a biopsy or surgery. Several laboratory methods may be used.

Common testing methods include:

• Immunohistochemistry, which detects the BCL6 protein inside tumour cell nuclei.

• Fluorescence in situ hybridization (FISH), which looks for rearrangements of the BCL6 gene.

• Molecular testing, such as next-generation sequencing, in selected cases.

Immunohistochemistry is most commonly used for initial evaluation, while FISH is often added when a high-grade lymphoma is suspected.

How do BCL6 results appear in a pathology report?

BCL6 results are usually found in sections of the pathology report labeled immunohistochemistry, biomarker studies, or molecular testing.

Results may be reported as:

• BCL6 positive, meaning the protein is present in tumour cell nuclei.

• BCL6 negative, meaning the protein is not detected.

• BCL6 rearrangement detected, if a gene rearrangement is found.

• No BCL6 rearrangement detected, if genetic testing is negative.

The report may also include a comment explaining how the BCL6 result supports a specific lymphoma diagnosis or whether it contributes to classification as a high-grade or aggressive lymphoma.

How does BCL6 fit with other lymphoma biomarkers?

BCL6 is rarely interpreted on its own. Instead, pathologists examine BCL6 alongside other lymphoma biomarkers to better understand where the tumour cells originate and how the lymphoma may behave.

BCL6 is commonly assessed alongside CD10 and MUM1, which help determine whether a lymphoma arises from germinal center B cells or from a later stage of B-cell development. This information is especially important in diffuse large B-cell lymphoma, where germinal center–type lymphomas generally have a better prognosis than nongerminal center types.

BCL6 is also frequently evaluated together with BCL2 and MYC. When rearrangements involving two or more of these genes are present, the lymphoma may be classified as a high-grade B-cell lymphoma, sometimes called a “double-hit” or “triple-hit” lymphoma. These lymphomas tend to behave more aggressively and are treated differently.

In some T-cell lymphomas, BCL6 is interpreted with other markers such as PD-1, ICOS, and CXCL13 to identify tumours that arise from follicular helper T cells.

By combining BCL6 results with other biomarkers, pathologists can provide a more precise diagnosis and classification, which helps guide prognosis and treatment planning.

Questions to ask your doctor

• Was my tumour tested for BCL6?

• What does my BCL6 result mean for the diagnosis?

• Does BCL6 affect how aggressive the cancer may be?

• Were other biomarkers, such as MYC or BCL2, tested at the same time?

• Do my BCL6 results influence treatment decisions?