BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

Niu, Yuna; Yang, Xue; Chen, Yifei; Zhang, Linbo; Jin, Xinyue; Tang, Y.; Li, Li; Yu, Li-Fang; Guo, Yilin; Wang, Hui

doi:10.1007/s12253-018-0476-7

Cited by 8 publications

(4 citation statements)

References 26 publications

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“…3C, chromosome conformation capture; LIF, leukemia inhibitory factor; PCR, polymerase chain reaction; TCGA, The Cancer Genome Atlas BCL3 is initially identified as a proto-oncogene in chronic lymphocytic leukemia with a critical role in regulating NF-κB signaling (Franzoso et al, 1992;McKeithan et al, 1990). Recently, increasing studies have reported that BCL-3 functions as a proto-oncogene in a wide range of human cancers including lung cancer (Dai et al, 2016;Dimitrakopoulos et al, 2015;Niu et al, 2019;Tu et al, 2016;Zhao et al, 2016). The BCL3 protein lacks DNA bind domain and primarily acts as a transcriptional co-regulator to modulate the NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

The enhancer rare germline variation rs548071605 contributes to lung cancer development

Wang

Yang

et al. 2021

Human Mutation

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Rare germline variations contribute to the missing heritability of human complex diseases including cancers. Given their very low frequency, discovering and testing disease‐causing rare germline variations remains challenging. The tag‐single nucleotide polymorphism rs17728461 in 22q12.2 is highly associated with lung cancer risk. Here, we identified a functional rare germline variation rs548071605 (A>G) in a p65‐responsive enhancer located within 22q12.2. The enhancer significantly promoted lung cancer cell proliferation in vitro and in a xenograft mouse model by upregulating the leukemia inhibitory factor (LIF) gene via the formation of a chromatin loop. Differential expression of LIF and its significant correlation with first progression survival time of patients further supported the lung cancer‐driving effects of the 22q‐Enh enhancer. Importantly, the rare variation was harbored in the p65 binding sequence and dramatically increased the enhancer activity by increasing responsiveness of the enhancer to p65 and B‐cell lymphoma 3 protein, an oncoprotein that assisted the p65 binding. Our study revealed a regulatory rare germline variation with a potential lung cancer‐driving role in the 22q12.2 risk region, providing intriguing clues for investigating the “missing heritability” of cancers, and also offered a useful experimental model for identifying causal rare variations.

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Section: Discussionmentioning

confidence: 99%

The enhancer rare germline variation rs548071605 contributes to lung cancer development

Wang

Yang

et al. 2021

Human Mutation

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“…Comparing all transcriptionally active genes from responders and non-responders, we identified 3212 differentially expressed genes (708 up-regulated genes and 2,504 downregulated genes in responders, Figure 2C). Several genes, such as MYC (31), XPO1 (32), RARA, BCL3 (33), and HDAC2 (34) showed lower expression in responders vs. nonresponders, whereas RORA was more expressed in responders (Figure 2D, Figure S2).…”

Section: Gene Expression Signature Of Patient Response To Atra-tcpmentioning

confidence: 99%

Clinical Responsiveness to All-trans Retinoic Acid Is Potentiated by LSD1 Inhibition and Associated with a Quiescent Transcriptome in Myeloid Malignancies

Tayari

Santos

Kwon

et al. 2021

Clinical Cancer Research

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In preclinical studies, the LSD1 inhibitor tranylcypromine (TCP) combined with alltrans retinoic acid (ATRA) induces differentiation and impairs survival of myeloid blasts in non-APL acute myeloid leukemia (AML). We conducted a Phase I clinical trial (NCT02273102) to evaluate the safety and activity of ATRA plus TCP in patients with relapsed/refractory AML and myelodysplasia (MDS).Experimental Design: Seventeen patients were treated with ATRA and TCP (3 dose levels: 10 mg twice daily [BID], 20 mg BID, and 30 mg BID).Results: ATRA-TCP had an acceptable safety profile. The maximum tolerated dose of TCP was 20 mg BID. Best responses included 1 morphologic leukemia-free state, 1 marrow complete remission with hematologic improvement, 2 stable disease with hematologic improvement, and 2 stable disease. By intention-to-treat, the overall response rate was 23.5% and clinical benefit rate

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“…At present, more and more studies focus on the ability of Bcl-3 can regulate the function of various cells through the NF-kB signaling pathway. In humans, Bcl-3 is also related to the occurrence and development of many diseases and malignant tumors, such as various inflammatory (16)(17)(18)(19) and autoimmune diseases (20,21), blood tumors (22,23) and solid tumors (24)(25)(26)(27). Among them, Bcl-3's participation in the immune system and various inflammatory diseases have been studied to some extent, and this review will focus on the inflammatory and immune diseases, exploring the current knowledge in this field.…”

Section: Introductionmentioning

confidence: 99%

Bcl-3: A Double-Edged Sword in Immune Cells and Inflammation

et al. 2022

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The NF-κB transcription factor family controls the transcription of many genes and regulates a number of pivotal biological processes. Its activity is regulated by the IκB family of proteins. Bcl-3 is an atypical member of the IκB protein family that regulates the activity of nuclear factor NF-κB. It can promote or inhibit the expression of NF-κB target genes according to the received cell type and stimulation, impacting various cell functions, such as proliferation and differentiation, induction of apoptosis and immune response. Bcl-3 is also regarded as an environment-dependent cell response regulator that has dual roles in the development of B cells and the differentiation, survival and proliferation of Th cells. Moreover, it also showed a contradictory role in inflammation. At present, in addition to the work aimed at studying the molecular mechanism of Bcl-3, an increasing number of studies have focused on the effects of Bcl-3 on inflammation, immunity and malignant tumors in vivo. In this review, we focus on the latest progress of Bcl-3 in the regulation of the NF-κB pathway and its extensive physiological role in inflammation and immune cells, which may help to provide new ideas and targets for the early diagnosis or targeted treatment of various inflammatory diseases, immunodeficiency diseases and malignant tumors.

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BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

Cited by 8 publications

References 26 publications

The enhancer rare germline variation rs548071605 contributes to lung cancer development

The enhancer rare germline variation rs548071605 contributes to lung cancer development

Clinical Responsiveness to All-trans Retinoic Acid Is Potentiated by LSD1 Inhibition and Associated with a Quiescent Transcriptome in Myeloid Malignancies

Bcl-3: A Double-Edged Sword in Immune Cells and Inflammation

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