BCL11A: a potential diagnostic biomarker and therapeutic target in human diseases

Yin, Jiawei; Xie, Xiaoli; Ye, Yufu; Wang, Limin; Che, Fengyuan

doi:10.1042/bsr20190604

Cited by 45 publications

(51 citation statements)

References 105 publications

(137 reference statements)

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“…The deletion of CDKN2A has been associated with poor survival of affected glioma patients [ 53 , 54 ]. BCL11A is mainly known as a transcriptional repressor important for brain development [ 55 ]. COL1A1 has been shown to be involved in cell invasion [ 56 ], and MET is an important factor involved in a variety of processes that contribute to the malignancy of gliomas [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Astrocytoma Progression Towards Secondary Glioblastomas Utilizing Patient-Matched Tumor Pairs

Seifert

Schackert

Temme

et al. 2020

Cancers

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Astrocytomas are primary human brain tumors including diffuse or anaplastic astrocytomas that develop towards secondary glioblastomas over time. However, only little is known about molecular alterations that drive this progression. We measured multi-omics profiles of patient-matched astrocytoma pairs of initial and recurrent tumors from 22 patients to identify molecular alterations associated with tumor progression. Gene copy number profiles formed three major subcluters, but more than half of the patient-matched astrocytoma pairs differed in their gene copy number profiles like astrocytomas from different patients. Chromosome 10 deletions were not observed for diffuse astrocytomas, but occurred in corresponding recurrent tumors. Gene expression profiles formed three other major subclusters and patient-matched expression profiles were much more heterogeneous than their copy number profiles. Still, recurrent tumors showed a strong tendency to switch to the mesenchymal subtype. The direct progression of diffuse astrocytomas to secondary glioblastomas showed the largest number of transcriptional changes. Astrocytoma progression groups were further distinguished by signaling pathway expression signatures affecting cell division, interaction and differentiation. As expected, IDH1 was most frequently mutated closely followed by TP53, but also MUC4 involved in the regulation of apoptosis and proliferation was frequently mutated. Astrocytoma progression groups differed in their mutation frequencies of these three genes. Overall, patient-matched astrocytomas can differ substantially within and between patients, but still molecular signatures associated with the progression to secondary glioblastomas exist and should be analyzed for their potential clinical relevance in future studies.

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Astrocytoma Progression Towards Secondary Glioblastomas Utilizing Patient-Matched Tumor Pairs

Seifert

Schackert

Temme

et al. 2020

Cancers

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“…In addition, we determined that 4 out of 5 of these genes ( GAB1 , CIITA, HLA-DQA1, HLA-DQB1) are predicted to be gene targets of the BCL11A transcription factor. BCL11A is a zinc finger protein that is expressed in hematopoietic cells and in the brain and whose presence is linked to hematological malignancies 41, 70 . This TF has been shown to play an important role in lymphoid development.…”

Section: Discussionmentioning

confidence: 99%

Identification of new therapeutic targets inCRLF2-overexpressing B-ALL through discovery of TF-gene regulatory interactions

Badri

Carella

Lhoumaud

et al. 2019

Preprint

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CRLF2 overexpression in B-ALL patients with an IGH-CRLF2 translocation activates JAK-STAT, PI3K and ERK/MAPK signaling pathways. Although inhibitors of these pathways are available, investigating alternate targets could reduce treatment-associated toxicities.Comparing RNA-seq from IGH-CRLF2 and non-translocated patients we defined a translocation gene signature. Next, we assembled a B-ALL cancer-specific regulatory network using 529 B-ALL patient samples from the NCI TARGET database coupled with priors generated from ATAC-seq peak TF-motif analysis. The network was used to infer differential changes in TF activities predicted to control IGH-CRLF2 deregulated genes, thereby enabling identification of translocation-associated pathways and potential new therapeutic targets.

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“…In addition, BCL11A is highly expressed in some haematological malignancies and malignant solid tumours and is associated with poor clinical prognosis 1 .We have previously shown that BCL11A is a triple negative breast cancer (TNBC) gene 12 . BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC), and its genomic locus is amplified in up to 38% of BLBC.…”

Section: Introductionmentioning

confidence: 99%

“…The transcription factor B-cell lymphoma/leukaemia 11A (BCL11A) is a zinc finger protein mainly expressed in the brain and hematopoietic cell lineages 1,2 . BCL11A is part of the ATP-dependent chromatin remodelling mammalian SWI/SNF complex 3 , which enables nucleosome restructuring, ensuring DNA is accessible for transcription replication and DNA repair 4 .…”

Section: Introductionmentioning

confidence: 99%

“…Evidence is also accumulating of its role in various other physiological processes, including a developmental role in the skin and in determining dendritic cell fate 8,9 . It is also implicated in the 2p15-p16.1 microdeletion syndrome, characterised by intellectual disability, Type II diabetes and β-hemoglobinopathies, particularly sickle cell disease (SCD) 1 . Targeting BCL11a has been implemented to regulate foetal haemoglobin (HbF) levels in erythrocytes in a transgenic humanized sickle cell mouse model and in SCD patients, thus providing preliminary evidence of the therapeutic effects of such a strategy for β-hemoglobinopathies 10,11 .…”

Section: Introductionmentioning

confidence: 99%

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The generation of a Bcl11a lineage tracing mouse model

Pensa

Khaled

2021

Preprint

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The transcription factor B-cell lymphoma/leukaemia 11A (BCL11A) has essential functions in physiological processes as well as haematological and solid malignancies, however, its contribution to tissue development and tumour progression is poorly understood. Here we show the generation of a Bcl11a lineage tracing mouse model to allow for in vivo tracking of Bcl11a-expressing cells and their progeny. We validate the model in the mammary gland by using flow cytometry and whole-tissue 3D imaging to locate labelled cells after induction of tracing in early development. We show that Bcl11a is predominantly expressed in long-lived luminal progenitors which populate mammary alveoli upon pregnancy, confirming bona fide labelling of Bcl11a cells. The Bcl11a lineage tracing mouse model therefore provides a powerful resource to study Bcl11a cells in development, homeostasis, and cancer.

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BCL11A: a potential diagnostic biomarker and therapeutic target in human diseases

Cited by 45 publications

References 105 publications

Molecular Characterization of Astrocytoma Progression Towards Secondary Glioblastomas Utilizing Patient-Matched Tumor Pairs

Molecular Characterization of Astrocytoma Progression Towards Secondary Glioblastomas Utilizing Patient-Matched Tumor Pairs

Identification of new therapeutic targets inCRLF2-overexpressing B-ALL through discovery of TF-gene regulatory interactions

The generation of a Bcl11a lineage tracing mouse model

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