A novel TEL-AML1 fusion transcript involving the pro-apoptotic gene BCL-G in pediatric precursor B acute lymphoblastic leukemia

Abdelhaleem, Mohamed; Yi, Qiong; Beimnet, Kassa

doi:10.1038/sj.leu.2404249

Cited by 5 publications

(3 citation statements)

References 3 publications

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“…18 No mutations or expression changes of the Bcl-G gene were found in children with acute lymphoblastic leukaemia, 17 but a TEL–AML1 fusion transcript involving BCL-G was reported in another. 19 In breast cancer, Bcl-G expression was found to be abnormally reduced and possibly regulated post-translationally by maternal embryonic leucine zipper kinase, a recently identified protein kinase and candidate oncoprotein upregulated in several types of cancer. 20 In all these studies, BCL-G was considered a proapoptotic BH3-only protein and, as such, a potential tumour suppressor.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 family member Bcl-G is not a proapoptotic protein

et al. 2012

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The three major subgroups of the Bcl-2 family, including the prosurvival Bcl-2-like proteins, the proapoptotic Bcl-2 homology (BH)3-only proteins and Bax/Bak proteins, regulate the mitochondrial apoptotic pathway. In addition, some outliers within the Bcl-2 family do not fit into these subgroups. One of them, Bcl-G, has a BH2 and a BH3 region, and was proposed to trigger apoptosis. To investigate the physiological role of Bcl-G, we have inactivated the gene in the mouse and generated monoclonal antibodies to determine its expression. Although two isoforms of Bcl-G exist in human, only one is found in mice. mBcl-G is expressed in a range of epithelial as well as in dendritic cells. Loss of Bcl-G did not appear to affect any of these cell types. mBcl-G only binds weakly to prosurvival members of the Bcl-2 family, and in a manner that is independent of its BH3 domain. To understand what the physiological role of Bcl-G might be, we searched for Bcl-G-binding partners through immunoprecipitation/mass spectroscopy and yeast-two-hybrid screening. Although we did not uncover any Bcl-2 family member in these screens, we found that Bcl-G interacts specifically with proteins of the transport particle protein complex. We conclude that Bcl-G most probably does not function in the classical stress-induced apoptosis pathway, but rather has a role in protein trafficking inside the cell.

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Section: Discussionmentioning

confidence: 99%

Bcl-2 family member Bcl-G is not a proapoptotic protein

et al. 2012

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“…Allelic losses within chromosome 12 were also reported in patients with prostate cancer [ 60 , 61 ], oligodontia, and thrombocytopenia [ 62 ]. An in-frame insertion of the 33-nucleotide fragment derived from exon 4 of BCL2L14 corresponding to the median isoform was detected between exon 5 of TEL and exon 2 of AML1 , however, the functional consequences were not determined [ 63 ]. BCL2L14 was identified in a deleted region accompanying translocation leading to ETS variant transcription factor 6 (ETV6)-Runt-related transcription factor 1 (RUNX1) fusion protein in ALL cells [ 64 ].…”

Section: Disease-associated Genetic Alterations Of Bcl2l14mentioning

confidence: 99%

BCL-G: 20 years of research on a non-typical protein from the BCL-2 family

Hartman

Czyż

2023

Cell Death Differ

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Proteins from the BCL-2 family control cell survival and apoptosis in health and disease, and regulate apoptosis-unrelated cellular processes. BCL-Gonad (BCL-G, also known as BCL2-like 14) is a non-typical protein of the family as its long isoform (BCL-GL) consists of BH2 and BH3 domains without the BH1 motif. BCL-G is predominantly expressed in normal testes and different organs of the gastrointestinal tract. The complexity of regulatory mechanisms of BCL-G expression and post-translational modifications suggests that BCL-G may play distinct roles in different types of cells and disorders. While several genetic alterations of BCL2L14 have been reported, gene deletions and amplifications prevail, which is also confirmed by the analysis of sequencing data for different types of cancer. Although the studies validating the phenotypic consequences of genetic manipulations of BCL-G are limited, the role of BCL-G in apoptosis has been undermined. Recent studies using gene-perturbation approaches have revealed apoptosis-unrelated functions of BCL-G in intracellular trafficking, immunomodulation, and regulation of the mucin scaffolding network. These studies were, however, limited mainly to the role of BCL-G in the gastrointestinal tract. Therefore, further efforts using state-of-the-art methods and various types of cells are required to find out more about BCL-G activities. Deciphering the isoform-specific functions of BCL-G and the BCL-G interactome may result in the designing of novel therapeutic approaches, in which BCL-G activity will be either imitated using small-molecule BH3 mimetics or inhibited to counteract BCL-G upregulation. This review summarizes two decades of research on BCL-G.

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“…Note A novel TEL-AML1 fusion transcript, comprising an in-frame insertion of 33 nucleotides derived from BCL2L14 between exon 5 of TEL and exon 2 of AML1 has been described in a case of pediatric precursor B ALL (Abdelhaleem et al, 2006). This fusion transcript appears to be rare, and its biological effects are unknown.…”

Section: Precursor B Acute Lymphoblastic Leukemia (All)mentioning

confidence: 99%