Regulation of the Development and Function of B Cells by ZBTB Transcription Factors

Zhu, Can; Chen, Ge; Zhao, Ying; Gao, Xiao‐Ming; Wang, Jun

doi:10.3389/fimmu.2018.00580

Cited by 60 publications

(54 citation statements)

References 76 publications

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“…8 Within the B lineage, ZBTB20 is expressed in peritoneal B1 cells, germinal center B cells, and in longlived bone marrow plasma cells. 7 In B1 cells, ZBTB20 is highly expressed and promotes BLIMP1 expression and terminal B-cell differentiation, although PAX5 has also been shown to bind to the ZBTB20 promoter, suggesting that it may down-regulate ZBTB20 expression in immature B cells. 7,9 Aberrant ZBTB20 expression has been demonstrated in certain human B-cell lymphoma cell lines, suggesting that dysregulated expression could lead to tumorigenesis.…”

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confidence: 99%

“…7 In B1 cells, ZBTB20 is highly expressed and promotes BLIMP1 expression and terminal B-cell differentiation, although PAX5 has also been shown to bind to the ZBTB20 promoter, suggesting that it may down-regulate ZBTB20 expression in immature B cells. 7,9 Aberrant ZBTB20 expression has been demonstrated in certain human B-cell lymphoma cell lines, suggesting that dysregulated expression could lead to tumorigenesis. 8 However, whether loss of normal ZBTB20 function contributes to tumorigenesis of this B-ALL requires further investigation.…”

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confidence: 99%

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Identification of a Novel ZBTB20-JAK2 Fusion by Mate-Pair Sequencing in a Young Adult With B-Lymphoblastic Leukemia/Lymphoma

Peterson

Blackburn

Webley

et al. 2019

Mayo Clinic Proceedings

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involvement, and all had improvement in their symptoms. Other patients who had cutaneous and neurological involvement also had symptomatic improvements. The treatment was tolerated well, with only one patient discontinuing therapy because of headache. The performance status improved in 75% of patients, and the median survival for the cohort was 24 months. It is likely that etanercept had an effect on AL amyloidosis, but appropriate response assessment using free light chains and cardiac biomarkers was not available. To our knowledge, this is the first report of a patient with AL amyloidosis and symptoms related to GI involvement responding to therapy with adalimumab. Tumor necrosis factor a could play a role in the pathophysiology of AL amyloidosis. In our patient, diarrhea and severe abdominal pain improved dramatically after receiving a total dose of 80 mg of adalimumab subcutaneously. The effectiveness of this agent could be investigated further in phase I/II trials in patients with refractory AL amyloidosis.

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confidence: 99%

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Identification of a Novel ZBTB20-JAK2 Fusion by Mate-Pair Sequencing in a Young Adult With B-Lymphoblastic Leukemia/Lymphoma

Peterson

Blackburn

Webley

et al. 2019

Mayo Clinic Proceedings

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“…The predicted chimeric protein contains one dimerizing BTB/POZ domain and one zinc-finger-C2H2 domain of ZBTB20 at the amino terminus fused with the JAK2-tyrosine-kinase domain ( Fig. 2E), allowing for constitutive activation of ZBTB20-JAK2 fusion protein through partner-mediated oligomerization, similar to other known kinase-activating JAK2 gene fusions (Roberts et al 2014;Maeda 2016;Zhu et al 2018). Furthermore, the cytogenomic array identified a deep 107-kB deletion at Chromosome 7p12, consistent with a homozygous IKZF1 deletion (data not shown).…”

Section: Genomic Analysismentioning

confidence: 87%

“…ZBTB20-JAK2 gene fusion in myeloid/lymphoid neoplasm with eosinophilia presenting as B-ALL An in-frame fusion between ZBTB20 exon 4 as the 5 ′ partner (ZBTB20:NM_00116342 [exon:4] Chr 3:114069121) and JAK2 exon19 as the 3 ′ partner (JAK2:NM_004972 [exon:19] Chr 9:5081725) was identified using the Archer next-generation sequencing (NGS) assay and analysis based on human genome assembly version hg19 (see Table 1) . ZBTB20 is reportedly expressed in germinal center B cells, plasma cells, and neuronal tissues, but the expression in myeloid/erythroid precursors remains unknown (Chevrier et al 2014;Wang and Bhattacharya 2014;Maeda 2016;Zhu et al 2018). Expression of ZBTB20-JAK2 RNA chimeric transcripts was confirmed by Sanger sequencing on cDNA amplicons (Fig.…”

Section: Genomic Analysismentioning

confidence: 88%

The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia

Lee

Pfau

Choi

et al. 2020

Cold Spring Harb Mol Case Stud

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We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome-like BALL (Ph-like BALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like BALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like BALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between BALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.

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“…This gene encodes a transcription factor. Several proteins in the ZBTB family have emerged as critical factors that regulate the lineage commitment, differentiation, and function of lymphoid cells as well as many other developmental events [61]. ZBTB2 is among the master regulators of the p53 pathway [29].…”

Section: Density-plots Revealed Candidate Icrs For Potential Imprintementioning

confidence: 99%

Discovering candidate imprinted genes and Imprinting Control Regions in the human genome

Bina

2019

Preprint

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Genomic imprinting is a process thereby a subset of genes is expressed in a parent-of-origin specific manner. This evolutionary novelty is restricted to mammals and controlled by genomic DNA segments known as Imprinting Control Regions (ICRs). The known imprinted genes function in many important developmental and postnatal processes including organogenesis, neurogenesis, and fertility. Furthermore, defects in imprinted genes could cause severe diseases and abnormalities. Because of the importance of the ICRs to the regulation of parent-of-origin specific gene expression, I developed a genome-wide strategy for their localization. This strategy located clusters of the ZFBS-Morph overlaps along the entire human genome. Previously, I showed that in the mouse genome, clusters of 2 or more of these overlaps correctly located ~ 90% of the fully characterized ICRs and germline Differentially Methylated Regions (gDMRs). The ZFBS-Morph overlaps are composite-DNA-elements comprised of the ZFP57 binding site (ZFBS) overlapping a subset of the MLL1 morphemes. My strategy consists of creating plots to display the density of ZFBS-Morph overlaps along genomic DNA. Peaks in these plots pinpointed several of the known ICRs/gDMRs within relatively long genomic DNA sections and even along entire chromosomal DNA. Therefore, peaks in the density-plots are likely to reflect the positions of known or candidate ICRs. I also found that by locating the genes in the vicinity of candidate ICRs, I could discover potential and novel human imprinting genes. Additionally, my exploratory assessments revealed a connection between several of the potential imprinted genes and human developmental anomalies including syndromes. ____________________________________________________________________________

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Regulation of the Development and Function of B Cells by ZBTB Transcription Factors

Cited by 60 publications

References 76 publications

Identification of a Novel ZBTB20-JAK2 Fusion by Mate-Pair Sequencing in a Young Adult With B-Lymphoblastic Leukemia/Lymphoma

Identification of a Novel ZBTB20-JAK2 Fusion by Mate-Pair Sequencing in a Young Adult With B-Lymphoblastic Leukemia/Lymphoma

The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia

Discovering candidate imprinted genes and Imprinting Control Regions in the human genome

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