BCL6 (B-Cell Lymphoma 6)

2012-12-01   Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
3q27.3
IMAGE
Atlas Image
LEGEND
BCL6 (3q27) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
IMAGE
Atlas Image
LEGEND
BCL6 (B-Cell Lymphoma 6) Hybridization with Vysis break apart probe (Abbott Molecular, US) showing BCL6 on 3q27.3 (red-green or a fused yellow signal) - Courtesy Adriana Zamecnikova.
LOCUSID
ALIAS
BCL5,BCL6A,LAZ3,ZBTB27,ZNF51
FUSION GENES

DNA/RNA

Atlas Image

Description

The gene is encoded by 11 exons that are located on chromosome 3q27 and is 24,3 kb. The 5 portion encodes for the BTB/POZ domain (broad-complex/tramtrack/bric-a-brac/pox virus/zinc finger), while the 3 end encodes for 6 DNA binding zinc fingers. The first ATG occurs in exon 3.

Transcription

3,8 kb mRNA.

Proteins

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Description

The protein product is 706 amino acids with an estimated molecular weight of 78,8 kDa.

Expression

Normally expressed in germinal center B and T cells, other lymphoid tissues, in skeletal muscle cells and in keratinocytes. Normally expressed in germinal center B and T cells, other lymphoid tissues, in skeletal muscle cells and in keratinocytes.

Localisation

Nuclear paraspeckles/dots.
Atlas Image

Function

Protein domains and functions
The protein can bind to sequence specific DNA and repress its transcription in addition to recruiting other protein repressors. The DNA binding is mediated through the consensus sequence TTCCT(A/C)GAA (see below), while the protein-protein interactions are mediated through the BTB/POZ domain and it has been shown to interact with other zinc finger proteins and corepressors (including Histone Deacetylase 1 (HDAC1) and NCOR2 (Silencing Mediator of Retinoid and Thryoid Receptor 1 (SMRT1))). The carboxy terminus, on the other hand, is responsible for sequence specific DNA binding through its 6 zinc fingers.

Consensus DNA motifs recognized by BCL6
The Zn fingers of BCL6 binds to DNA and recognizes specific DNA motifs: the M00424 motif, a consensus sequence for the NKX-homeobox family of transcription factors, the M2 motif, which mimics an M00424 half site; and the M0 motif (see details in Basso et al., 2010).

BCL6 cellular function
- BCL6 cellular function in germinal centers of lymph nodes follicles
Mature naïve B cells migrate from the bone marrow to lymphoid nodes, meet the antigen, they are stimulated to proliferate and further differentiate into centroblasts in germinal centers (GC) of lymphoid follicles. There, cells are subjects to somatic hypermutation and class switch recombination, to further differenciate into memory B cells or plasma cells. This process also requires the presence of follicular helper T cells. BCL6 has a major role in this process. In particular, BCL6 prevents ATM and TP53 (Phan et al., 2004) to induce apoptosis in response to DNA rearrangements such as those necessary for somatic hypermutation and class switch recombination processes. BCL6 is therefore essential for normal B cell development (reviews in Albagli-Curiel, 2003; Jardin et al., 2007; Parekh et al., 2008; Basso and Dalla-Favera, 2010; Pellicano and Holyoake, 2011; Wagner et al., 2011; Basso and Dalla-Favera, 2012; Okada et al., 2012).
- T follicular helper cells
BCL6 is essential for the development of follicular helper T (Tfh) cells. Tfh cells are defined by the expression of the surface markers CXCR5 and PD-1 and synthesis of IL4 and IL21. BCL6 upregulation of B cells in the outer follicle sustains their interactions with helper T cells and allows them to enter the germinal centers (GC) region (Poholek et al., 2010; Kitano et al., 2011; Baumjohann et al., 2011). ICOS induces BCL6, and BCL6 then induces CXCR5. Tfh cells were lost in the absence of B cells, demonstrating a B cell requirement for maintenance of BCL6 and Tfh cell commitment (Choi et al., 2011). BCL6 and MAF cooperate to induce Tfh cell differentiation (Kroenke et al., 2012).
- Other tissues
BCL6 promotes survival of olfactory sensory neurons (Otaki etal., 2010).
BCL6 associate to NACC1 in brain regions (Korutla et al., 2009).
BCL6 forms a complex with BCOR on the promoters of Notch target genes in Xenopus embryos (Sakano et al., 2010).
BCL6-overexpression inhibits osteoclastogenesis, and the PRDM1 (Blimp-1)/BCL6 balance is essential in regulating the bone homeostasis by controlling osteoclastogenesis (Miyauchi et al., 2010).
BCL6 controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation in pulmonary epithelium (Seto et al. 2011).

BCL6 repression activity
BCL6 binds to DNA as a homodimer and recruits co-repressor molecules, which, in turn, recruit class I and II histone deacetylases. BCL6 and histone deacetylases (HDACs) form stable complexes. BCL6 binds HDACs both directly through its C-terminal Zn fingers and through its N-terminal BTB/POZ domain and indirectly by recruiting several co-repressors such as BCOR, NCOR1, NCOR2 (which bind in a mutually exclusive way to the BTB/POZ domain), CTBP1 (which binds the BTB/POZ and the PEST domains), and MTA3 (which binds the PEST domain). Deacetylation of histones leads to transcriptional repression of BCL6 targets.
BCL6 interacts with ZBTB17 to repress CDKN1A and BCL2 (Phan et al., 2005). BCL6 has also been found to interact with other POK family members ((POZ and Krüppel)/ZBTB (zing finger and BTB) protein family) such as ZBTB7A (LRF) and ZBTB16 (PLZF).

BCL6 targets
An integrated biochemical and computational approach has recently identified thousands of BCL6 direct target genes, including B cell receptor (BCR; note: nothing to do with BCR, the partner of ABL1) and CD40 signaling genes (involved in signal transduction, MAPK activation, NF-AT activation, and NF-kB activation); T cell-mediated B-cell activation; apoptosis (BCL2, proteins involved in positive and negative regulation of the DISC complex and caspase activation, suggesting a role for BCL6 in balancing pro- and antiapoptotic programs in GC B cells); response to DNA damage (ATM, TP53, CDKN1A, ATR, CHEK1, TP53BP1...); interferon and cytokine signaling (interferon-type and interleukin receptors that lead to activation of JAK/STAT. STAT1, STAT3, and STAT5A were also found to be directly repressed by BCL6); Toll-like receptor signaling; TGFb receptor signaling; and WNT signaling (Basso et al., 2010).

BCL6 regulation
- B cell receptor
B cell receptor (BCR) induces BCL6 phosphorylation by MAPK1 on Ser333 and Ser343, which targets BCL-6 for rapid degradation by the ubiquitin/proteasome pathway (Niu et al., 1998). FBXO11 promotes BCL6 ubiquitylation and degradation (Duan et al., 2012).
- DNA damage
After DNA damage, the kinase ATM promotes BCL6 phosphorylation; follows an interaction with PIN1 required for BCL6 degradation (Phan et al., 2007).
- EP300
EP300 binds and acetylates BCL6, which inactivates BCL6 (acetylation disrupts the ability of BCL6 to recruit histone deacetylases). The same two pathways (HDAC pathway and SIRT2 pathway) that regulate acetylation-mediated activation of TP53 also control acetylation-mediated inactivation of BCL6 (Bereshchenko et al., 2002). BCL6 represses the expression of EP300 and its cofactor BAT3 (Cerchietti et al., 2010). EP300 acetylates and activates PAX5 (He et al., 2011), which enhances BCL6.
- Autoregulation
BCL6 protein binds BCL6 gene promoter, and repress BCL6, mechanism of negative autoregulation (Pasqualucci et al., 2003). PATZ1 interacts with BCL6 and is required for its negative autoregulation (Pero et al., 2012).
- CD40 signaling
CD40 signaling activates various pathways, including NF-kB, NF-AT, and AP-1 (Francis et al., 1995). ILF2 (NF45) and ILF3 (NF90) form the nuclear factor of activated T-cells (NF-AT), a crucial transcription factor essential for productive T cell activation (Kao et al., 1994). CD40 signalling reduces BCL6 expression, through induction of IRF4 by the NF-kB pathway (Saito et al., 2007).
- PRDM1 (review in Crotty et al., 2010)
JUND/AP-1 and activated STATs drive high BCL6 expression in GC B cells (Arguni et al., 2006). STAT5 up-regulates BCL6 expression (Scheeren et al., 2005); in contrast, STAT3 up-regulates PRDM1 (Diehl et al., 2008) (the protein coded from PRDM1 is named Blimp-1). BCL6 directly promotes the expression of BACH2, which repress PRDM1 (Blimp-1). BCL6 also suppresses PRDM1 (Blimp-1) through repression of IRF4. IRF4 binds to and induces PRDM1. PRDM1 (Blimp-1) abrogates BCL6. PAX5 (protein name: BSAP) contributes to BCL6 expression (Nera et al., 2006; Tarlinton, 2011). PAX5 abrogates PRDM1 (Blimp-1), which abrogates PAX5. BCL6 and PAX5 promote the expression of AICDA and UNG (which have a major role in somatic hypermutation and class-switch recombination) (Alinikula et al., 2011). BCL6 positively regulates AICDA, IRF8, and MYB via repression of MIR155 (Basso et al., 2012). BCL6 mediates transcriptional repression by recruiting HDACs. MIR155 directly targets HDAC4 and indirectly attenuates BCL6 expression (Sandhu et al., 2012). PRDM1 (Blimp-1) represses BCL6, and also PAX5, MYC, and AICDA (review in Martins and Calame, 2008). IRF8 is expressed at the high levels in germinal center (GC) B cells. IRF8 binds BCL6 promoter and activates BCL6 (Lee et al., 2006).
It is also to be noted that IRF4 is involved in the t(6;14)(p25;q32) IRF4/IGH. PRDM1 (Blimp-1) is inactivated in about 50% of the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (ABC- DLBCL) (Mandelbaum et al., 2010).

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Homology

BTB/POZ - Zinc Finger proteins (PLZF, HIC1, KUP, BAZF, ttk (drosophila), BrC (drosophila)...).

Mutations

Note

Chromosomal translocations involving BCL6 are found in 40% of diffuse large B-cell lymphomas (DLBCL), 5-10% of follicular lymphomas (FL), and 50% of nodular lymphocyte predominant Hodgkin lymphomas.
Mutations in the autoregulatory region of BCL6 leads to a constitutive BCL6 expression (Pasqualucci et al., 2003).
IRF4 response elements in the BCL6 gene mediate repression of BCL6. Mutations in the IRF4 repression region of BCL6 gene also leads to constitutive expression of BCL6 (Saito et al., 2007).
MYC, BCL2, and BCL6 rearrangements were detected in 6%, 15%, and 29% respectively of diffuse large B-cell lymphoma (DLBCL) patients. Double or triple rearrangements were detected in 3% of these patients. MYC rearrangement was associated with a significantly worse overall survival. BCL6 rearrangement also predicted a significantly shorter overall survival, especially for the non-GC phenotype (Akyurek et al., 2012).
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Implicated in

Disease
B cell non-Hodgkin Lymphoma (B-NHL)
Prognosis
Generally considered to be a better prognosis if there is increased expression of BCL6. The mechanism by which its expression is increased does not seem to matter (ie different translocation partners increasing its expression results in the same prognosis).
Cytogenetics
3q27 rearrangements/aberrations are diverse and include: translocations, micro-deletions, point mutations and hypermutation. Approximately 50% of 3q27 translocations involves Ig genes at 14q32 (IgH), 2p12 (IgK) and 22q12 (IgL) (e.g. t(3;14)(q27;q32)). Less than half (~40%) include a variety of other chromosomal regions (1q21, 2q21, 4p11, 5q31, 6p21, 7p12, 8q24, 9p13, 11q13, 11q23, 12q11, 13q14-21, 14q11, 15q21; 16p11...). In addition, there are frequent bi-allelic alterations (translocation and deletion or mutation on the non-translocated allele).
Hybrid gene
hybrid gene and transcripts are formed following promoter substitution between BCL6 and its different partners. Chimeric transcripts are generally detected containing the 5 part of the gene partner fused to the normal BCL6 exon 2 splice acceptor site. In some cases reciprocal chimeric transcripts driven by the 5 regulatory region of BCL6 fused to the partner gene coding region, have been characterised.
- t(3;22)(q27;q11) the gene in 22q11 is IGL
Fusion protein
No fusion protein.
Entity name
t(9;22)(q34;q11) leukemias
Disease
BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition (Duy et al. 2011).
In chronic myelogenous leukemia (CML), BCL6 acts as a critical effector downstream of FoxO in self-renewal signaling of CML-initiating cells. Therefore, pharmacological inhibition of BCL6 may represent a novel strategy to eradicate leukemia-initiating cells in CML (Hurtz et al., 2011).
Entity name
Breast cancer
Disease
BCL6 protein is elevated in human breast cancers, especially in high-grade, poorly differentiated and metastatic breast cancer cases (Bos et al., 2003; Logarajah et al., 2003; Brill et al., 2010). PRL (prolactin) rapidly suppressed BCL6. Loss of PRL-STAT5a signaling and concomitant upregulation of BCL6 may represent a regulatory switch facilitating undifferentiated histology and poor prognosis (Brill et al., 2010).
Entity name
Bladder transitional cell carcinoma
Disease
BCL6 protein overexpression is observed in half of the cases of transitional cell carcinoma. However, BCL6 over-expression has a negative correlation with the histological grade (Cho et al., 2007).
Entity name
Soft tissue tumors
Disease
BCL6 expression is more frequent in malignant compared with benign/uncertain solitary fibrous tumors, as well as in leiomyosarcomas compared with leiomyomas (Walters et al., 2011).
Entity name
Neuroblastoma
Disease
In the neuroblastic phenotype of neuroblastoma, BCL6 expression is associated with increased time to relapse and increased overall survival (Chamdin et al., 2009).
Entity name
Gastric cancer
Disease
In a study of 100 gastric cancer cases, BCL6 was highly expressed in differentiated cancers and reduced or absent in undifferentiated cancers. However, survival was identical in BCL6-positive and BCL6-negative cases (Hirata et al., 2009).
Entity name
Disease
IL6 induces transcriptional up-regulation of BCL6 via JAK/STAT3 pathway. TNF (TNF alpha) up-regulates BCL6. BCL6 expression is mediated independantly via both JAK/STAT3 and NF-KB pathways in multiple myeloma cells (Hideshima et al., 2010).

Breakpoints

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Note

Clustered in a 3,3 kb EcoRI fragment (MTC) includind exon 1A and intron 1.

Bibliography

Pubmed IDLast YearTitleAuthors
222133942012Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.Akyurek N et al
125550642003Ambivalent role of BCL6 in cell survival and transformation.Albagli-Curiel O et al
216744822011Alternate pathways for Bcl6-mediated regulation of B cell to plasma cell differentiation.Alinikula J et al
167021652006JunD/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells.Arguni E et al
225008402012Roles of BCL6 in normal and transformed germinal center B cells.Basso K et al
199656332010Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells.Basso K et al
231663562012BCL6 positively regulates AID and germinal center gene expression via repression of miR-155.Basso K et al
218040142011Cutting Edge: Distinct waves of BCL6 expression during T follicular helper cell development.Baumjohann D et al
124020372002Acetylation inactivates the transcriptional repressor BCL6.Bereshchenko OR et al
210419532010BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy.Cerchietti LC et al
197014972009Bcl6 is expressed in neuroblastoma: tumor cell type-specific expression predicts outcome.Chamdin A et al
167726022006High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma.Chen YW et al
175424092007BCL6 gene mutations in transitional cell carcinomas.Cho HY et al
216362962011ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6.Choi YS et al
200840692010Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation.Crotty S et al
183542042008STAT3-mediated up-regulation of BLIMP1 Is coordinated with BCL6 down-regulation to control human plasma cell differentiation.Diehl SA et al
221136142012FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas.Duan S et al
215938722011BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition.Duy C et al
75375321995Induction of the transcription factors NF-kappa B, AP-1 and NF-AT during B cell stimulation through the CD40 receptor.Francis DA et al
213574262011Histone acetyltransferase p300 acetylates Pax5 and strongly enhances Pax5-mediated transcriptional activity.He T et al
202282722010A proto-oncogene BCL6 is up-regulated in the bone marrow microenvironment in multiple myeloma cells.Hideshima T et al
193372542009BCL6 degradation caused by the interaction with the C-terminus of pro-HB-EGF induces cyclin D2 expression in gastric cancers.Hirata Y et al
219114232011BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia.Hurtz C et al
75196131994Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90.Kao PN et al
168678732006Intrachromosomal rearrangement of chromosome 3q27: an under recognized mechanism of BCL6 translocation in B-cell non-Hodgkin lymphoma.Keller CE et al
82204271993LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas.Kerckaert JP et al
216362942011Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity.Kitano M et al
191213542009NAC1, a POZ/BTB protein that functions as a corepressor.Korutla L et al
224276372012Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation.Kroenke MA et al
163805102006Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein.Lee CH et al
129449042003BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation.Logarajah S et al
211562812010BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma.Mandelbaum J et al
183709212008Regulation and functions of Blimp-1 in T and B lymphocytes.Martins G et al
82747401994Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Krüppel-like zinc-finger protein.Miki T et al
203685792010The Blimp1-Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis.Miyauchi Y et al
165460972006Loss of Pax5 promotes plasma cell differentiation.Nera KP et al
171970222007Prognostic impact of chromosomal alteration of 3q27 on nodal B-cell lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 329 consecutive patients.Niitsu N et al
96495001998Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor.Niu H et al
171429542006Pathogenetic and clinical implications of non-immunoglobulin ; BCL6 translocations in B-cell non-Hodgkin's lymphoma.Ohno H et al
225008362012Differentiation of germinal center B cells and follicular helper T cells as viewed by tracking Bcl6 expression dynamics.Okada T et al
201514612010The proto-oncogene BCL6 promotes survival of olfactory sensory neurons.Otaki JM et al
184520902008Therapeutic targeting of the BCL6 oncogene for diffuse large B-cell lymphomas.Parekh S et al
125157142003Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma.Pasqualucci L et al
220254992011Assembling defenses against therapy-resistant leukemic stem cells: Bcl6 joins the ranks.Pellicano F et al
224934802012POZ-, AT-hook-, and zinc finger-containing protein (PATZ) interacts with human oncogene B cell lymphoma 6 (BCL6) and is required for its negative autoregulation.Pero R et al
155779132004The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.Phan RT et al
178282692007Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells.Phan RT et al
205196432010In vivo regulation of Bcl6 and T follicular helper cell development.Poholek AC et al
177852082007A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma.Saito M et al
202307512010BCL6 canalizes Notch-dependent transcription, excluding Mastermind-like1 from selected target genes during left-right patterning.Sakano D et al
157115482005STAT5 regulates the self-renewal capacity and differentiation of human memory B cells and controls Bcl-6 expression.Scheeren FA et al
218012482011Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation.Seto T et al
171753832007A novel t(2;3)(p11;q27) in a case of follicular lymphoma.Tapinassi C et al
217928742011Bcl6: where too much complexity is barely enough.Tarlinton DM et al
201244772010Prolactin inhibits BCL6 expression in breast cancer through a Stat5a-dependent mechanism.Tran TH et al
210836542011The role of BCL6 in lymphomas and routes to therapy.Wagner SD et al
217250422011BCL-6 expression in mesenchymal tumours: an immunohistochemical and fluorescence in situ hybridisation study.Walters MP et al
171753792007A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in a diffuse large B-cell lymphoma.Wang HY et al
82355961993Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma.Ye BH et al

Other Information

Locus ID:

NCBI: 604
MIM: 109565
HGNC: 1001
Ensembl: ENSG00000113916

Variants:

dbSNP: 604
ClinVar: 604
TCGA: ENSG00000113916
COSMIC: BCL6

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000113916ENST00000232014P41182
ENSG00000113916ENST00000406870P41182
ENSG00000113916ENST00000419510A0A0C4DH53
ENSG00000113916ENST00000430339C9JCS5
ENSG00000113916ENST00000438077C9JL16
ENSG00000113916ENST00000450123P41182
ENSG00000113916ENST00000621333P41182

Expression (GTEx)

0
50
100
150
200
250
300
350

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
FoxO signaling pathwayKEGGhsa04068
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Transcription of Cell Death GenesREACTOMER-HSA-5633008
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertainREACTOMER-HSA-6803205
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
167662632006Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.442
196315652009The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment.434
217854302011Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions.384
155779132004The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.221
224276372012Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation.151
177852082007A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma.135
233353692013MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma.130
169434292006Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets.129
175584102007Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR.111
221136142012FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas.97

Citation

Jean-Loup Huret

BCL6 (B-Cell Lymphoma 6)

Atlas Genet Cytogenet Oncol Haematol. 2012-12-01

Online version: http://atlasgeneticsoncology.org/gene/20/bcl6

Historical Card

2007-02-01 BCL6 (B-Cell Lymphoma 6) by  Stevan Knezevich 

BC Cancer Research Centre (BCCRC), Vancouver, British Columbia, Canada

1998-09-01 BCL6 (B-Cell Lymphoma 6) by  Jean-Pierre Kerckaert 

Unite 124 INSERM, Institut de Recherches sur le Cancer, Place de Verdun, 59045 Lille cedex, France