A <i>BACH2‐BCL2L1</i> fusion gene resulting from a t(6;20)(q15;q11.2) chromosomal translocation in the lymphoma cell line BLUE‐1

Türkmen, Seval; Riehn, Mathias; Klopocki, Eva; Molkentin, Mara; Reinhardt, Richard; Burmeister, Thomas

doi:10.1002/gcc.20863

Cited by 22 publications

(14 citation statements)

References 25 publications

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“…30 In addition, Burkitt lymphomas frequently express Bcl-x L , 46 and notably one such lymphoma was recently found to bear not only the hallmark MYC translocation but also a translocation of BCL-X that drove its high expression. 47 The BH3 mimetic ABT-737 48 and the closely related ABT-263 (navitoclax), 49 which target Bcl-2, Bcl-x L , and Bcl-w but not Mcl-1, are showing promise as anti-cancer agents. 14 Our results suggest that specific BH3 mimetic drugs could also prevent the development of certain types of tumors by unleashing the proapoptotic impetus of the oncogenic changes they have sustained (eg, deregulated c-Myc expression).…”

Section: Discussionmentioning

confidence: 99%

Endogenous Bcl-xL is essential for Myc-driven lymphomagenesis in mice

Kelly

Grabow

Delbridge

et al. 2011

Blood

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Impaired apoptosis is a cancer hallmark, and some types of lymphomas and other cancers harbor mutations that directly affect key cell death regulators, such as Bcl-2 family members. However, because the majority of tumors seem to lack such mutations, we are examining the hypothesis that tumorigenesis can be sustained at least initially by the normal expression of specific endogenous pro-survival Bcl-2 family members. We previously demonstrated that the lymphomagenesis in ⌭-myc transgenic mice, which constitutively overexpress the c-Myc oncoprotein in B-lymphoid cells and develop pre-B and B-cell lymphomas, does not require endogenous Bcl-2. In striking contrast, we report here that loss in these mice of its close relative Bcl- IntroductionImpaired apoptosis is considered a prerequisite for the development of most, if not all, cancers, 1-3 yet the mechanisms that promote the survival of most nascent malignant cells during the process of neoplastic transformation remain unknown. Apoptosis is regulated by opposing factions of the Bcl-2 family, which include both proteins essential for cell survival and those that drive cell death. 4,5 Despite very similar biochemical functions, the pro-survival family members (Bcl-2, Bcl-x L , Bcl-w, Mcl-1, and A1) have proven to have essential functions in specific cell types. 5 The critical initiators of apoptosis are the "BH3-only" proteins (eg, Bim, Puma, Bid), so-called because they share only a single Bcl-2 homology (BH) domain with other family members. They are activated by developmental cues and diverse stress stimuli, including cytokine deprivation, DNA damage and activation of oncogenes, such as c-Myc. 6-10 A second proapoptotic Bcl-2 sub-family, principally represented by the multi-BH domain proteins Bax and Bak, mediates the pivotal downstream step of mitochondrial outer membrane permeabilization (MOMP), which evokes activation of the caspase cascade that demolishes the cell. 4,11 The BH3-only proteins may provoke activation of Bax and Bak by their direct engagement, by sequestering pro-survival relatives or both ways. 4,5,[12][13][14] Studies using transgenic mice have established that overexpression of Bcl-2 15-18 or its antiapoptotic relatives, including and 20,21 or loss of proapoptotic Bcl-2 family members, such as Bim 10 or Puma, 22-24 contribute to tumor development, particularly in conjunction with mutations that deregulate cell cycle control, such as enforced c-Myc expression. Importantly, lymphomas evoked by combined overexpression of Bcl-2 and c-Myc require sustained Bcl-2 overexpression, 25 most likely to counter the apoptosis promoted by c-Myc overexpression under stress conditions, such as limiting supply of growth factors. [26][27][28][29] However, because only a proportion of cancers contain cytogenetic alterations (chromosomal translocations or somatically acquired copy number alterations) that directly promote the overexpression of Bcl-2 or one of its homologs, 2,3,30 we surmise that most cells undergoing neoplastic transformation are sustained (at ...

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Section: Discussionmentioning

confidence: 99%

Endogenous Bcl-xL is essential for Myc-driven lymphomagenesis in mice

Kelly

Grabow

Delbridge

et al. 2011

Blood

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“…Aberrations in the long arm of chromosome 6 are often associated with B cell malignancies. This includes a Bach2-Bcl2LI fusion product detected in a lymphoma line (12). This resulted in enhanced expression of the anti-apoptotic protein Bcl2LI (also known as BCL-XL).…”

Section: Bach2 In Diseasementioning

confidence: 99%

T Cell Fates Zipped Up: How the Bach2 Basic Leucine Zipper Transcriptional Repressor Directs T Cell Differentiation and Function

Richer

Lang

Butler

2016

The Journal of Immunology

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Recent data illustrate a key role for the transcriptional regulator Bach2 in orchestrating T cell differentiation and function. Although Bach2 has a well-described role in B cell differentiation, emerging data show that Bach2 is a prototypical member of a novel class of transcription factors that regulates transcriptional activity in T cells at super enhancers, or regions of high transcriptional activity. Accumulating data demonstrate specific roles for Bach2 in favoring regulatory T cell generation, restraining effector T cell differentiation and potentiating memory T cell development. Evidence suggests that Bach2 regulates various facets of T cell function by repressing other key transcriptional regulator such as Blimp-1. This review examines our current understanding of the role of Bach2 in T cell function and highlights the growing evidence that this transcriptional repressor functions as a key regulator involved in maintenance of T cell quiescence, T cell subset differentiation and memory T cell generation.

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“…Rearrangements of chromosome 20 observed in hPSCs are less frequently seen in cancers. Interestingly, there is one report of a translocation between chromosomes 20 and 6, resulting in a gene fusion between BACH2 and BCL2L1 leading to overexpression of BCL2L1 , the candidate gene in the 20q11.21 amplicon identified in hPSCs (Turkmen et al, 2011). This fusion was found in a cell line from a patient with relapsed high-grade B-cell lymphoma, which showed a particularly aggressive course.…”

Section: Parallels Of Genetic Changes In Hpscs With Human Germ Cell Tmentioning

confidence: 99%

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

Baker

Zhang

et al. 2014

Protein Cell

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Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving forces behind the genome evolution that may eventually lead to cancerous transformation.

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A BACH2‐BCL2L1 fusion gene resulting from a t(6;20)(q15;q11.2) chromosomal translocation in the lymphoma cell line BLUE‐1

Cited by 22 publications

References 25 publications

Endogenous Bcl-xL is essential for Myc-driven lymphomagenesis in mice

Endogenous Bcl-xL is essential for Myc-driven lymphomagenesis in mice

T Cell Fates Zipped Up: How the Bach2 Basic Leucine Zipper Transcriptional Repressor Directs T Cell Differentiation and Function

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

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