Burkitt's lymphoma

Molyneux, Elizabeth; Rochford, Rosemary; Griffin, Beverly E.; Newton, Robert; Jackson, Graham; Geetha, Menon; Harrison, Christine J.; Israëls, Trijn; Bailey, Simon

doi:10.1016/s0140-6736(11)61177-x

Cited by 526 publications

(509 citation statements)

References 136 publications

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“…Moreover, the COSMIC database (http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/) lists no mutations for TSC1 or TSC2 in Burkitt's lymphoma and they are not under the recurrently mutated genes in Burkitt's lymphoma identified by genomic approaches in two studies (Richter et al , 2012; Schmitz et al , 2012). Burkitt's lymphoma is an aggressively growing malignancy characterized by a MYC translocation that induces very high expression levels of the proto‐oncogenic transcription factor MYC (Molyneux et al , 2012). MYC promotes cell proliferation by multiple mechanisms including stimulation of cell cycle progression, ribosome biogenesis, tRNA synthesis, translation and metabolic adjustments to increase provision of metabolic intermediates (Dang, 2012).…”

Section: Introductionmentioning

confidence: 99%

Tuberous sclerosis complex is required for tumor maintenance in MYC‐driven Burkitt's lymphoma

et al. 2018

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The tuberous sclerosis complex (TSC) 1/2 is a negative regulator of the nutrient‐sensing kinase mechanistic target of rapamycin complex (mTORC1), and its function is generally associated with tumor suppression. Nevertheless, biallelic loss of function of TSC1 or TSC2 is rarely found in malignant tumors. Here, we show that TSC1/2 is highly expressed in Burkitt's lymphoma cell lines and patient samples of human Burkitt's lymphoma, a prototypical MYC‐driven cancer. Mechanistically, we show that MYC induces TSC1 expression by transcriptional activation of the TSC1 promoter and repression of miR‐15a. TSC1 knockdown results in elevated mTORC1‐dependent mitochondrial respiration enhanced ROS production and apoptosis. Moreover, TSC1 deficiency attenuates tumor growth in a xenograft mouse model. Our study reveals a novel role for TSC1 in securing homeostasis between MYC and mTORC1 that is required for cell survival and tumor maintenance in Burkitt's lymphoma. The study identifies TSC1/2 inhibition and/or mTORC1 hyperactivation as a novel therapeutic strategy for MYC‐driven cancers.

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Section: Introductionmentioning

confidence: 99%

Tuberous sclerosis complex is required for tumor maintenance in MYC‐driven Burkitt's lymphoma

et al. 2018

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“…Clinical treatment protocols in high-income countries are based on the FAB LMB study or the Berlin-Frankfurt-Muenster protocols and achieve outstanding overall survival rates in children (3). Nevertheless, there are cases of poor clinical outcome caused by the toxicity of the intensive chemotherapy, tumor lysis syndrome, or metastatic spread of lymphoma cells to the central nervous system (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, there are cases of poor clinical outcome caused by the toxicity of the intensive chemotherapy, tumor lysis syndrome, or metastatic spread of lymphoma cells to the central nervous system (4)(5)(6)(7). Especially elderly and HIV-positive patients show a poorer overall survival rate because of treatment-related mortality (3,8,9). Thus, there is the need to develop minimally toxic substances to treat patients with highgrade-non-Hodgkin lymphoma efficiently.…”

Section: Introductionmentioning

confidence: 99%

The NADPH Oxidase Inhibitor Imipramine-Blue in the Treatment of Burkitt Lymphoma

Klingenberg¹,

Becker²,

Eberth³

et al. 2014

Molecular Cancer Therapeutics

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Burkitt lymphoma is a rare malignancy arising from B cells. Current chemotherapeutic regimens achieve excellent overall survival rates in children, but less impressive rates in adults. There are cases with poor outcome caused by toxic effects of the therapy, tumor lysis syndrome, or metastatic spread of lymphomas to the central nervous system. Modulators of reactive oxygen species are currently discussed as potential drugs for the treatment of cancer. The NADPH oxidase 4 inhibitor imipramine-blue might satisfy the aforementioned requirements, and was studied here. We used MTT assay, crystal violet assay, and thymidine 3H-incorporation assay to analyze the effects of imipramine-blue on Burkitt lymphoma (BL2, BL2B95, BL30B95, BL41B95), neuroblastoma (KELLY, SH-SY5Y, SMS-KAN), cervix carcinoma (HeLa), breast cancer (MDA-MB231), angiosarcoma (AS-M), human embryonic kidney (HEK293WT), and nonmalignant (FLP1) cell lines. The effects of imipramine-blue on BL2B95 cells in vivo were investigated in xenografts on the chick chorioallantoic membrane (CAM). We report that imipramine-blue is a potent growth inhibitor for several cancer cell lines in vitro with IC 50 values comparable to those of doxorubicin (0.16-7.7 mmol/L). Tumor size of BL2B95 cells inoculated in the CAM was reduced significantly (P < 0.05) after treatment with 10 mmol/L imipramine-blue. Lymphogenic dissemination of BL2B95 and the formation of blood and lymphatic vessels in experimental tumors were not affected. We show that imipramine-blue can be used to decrease the viability of cancer cell lines in vitro and in vivo. Imipramine-blue reduces the size of experimental Burkitt lymphoma significantly but does not affect the dissemination of BL2B95 cells, angiogenesis, and lymphangiogenesis.

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“…MYC | lncRNA | cell cycle | B-cell lymphoma M YC is a transcription factor belonging to the basic helixloop-helix zipper family that was originally identified in Burkitt lymphoma (BL) because of a chromosomal translocation that juxtaposes the MYC oncogene with one of three immunoglobulin (Ig) loci (1)(2)(3). In BL, the deregulation of the oncogenic transcription factor MYC is considered to be the major driving force in lymphoma development (4,5).…”

mentioning

confidence: 99%

MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

Doose¹,

Haake

Bernhart³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.MYC | lncRNA | cell cycle | B-cell lymphoma M YC is a transcription factor belonging to the basic helixloop-helix zipper family that was originally identified in Burkitt lymphoma (BL) because of a chromosomal translocation that juxtaposes the MYC oncogene with one of three immunoglobulin (Ig) loci (1-3). In BL, the deregulation of the oncogenic transcription factor MYC is considered to be the major driving force in lymphoma development (4, 5). MYC overexpression is not restricted to BL and has been found to be a common feature SignificanceGains of the MYC gene are the most common imbalances in cancer and are associated with poor prognosis, particularly in B-cell lymphoma. Recent advances in DNA sequencing have revealed the existence of thousands of long noncoding RNAs (lncRNAs) with unknown functional relevance. We have here identified a MYC-regulated lncRNA that we named MYC-induced long noncoding RNA (MINCR) that has a strong correlation with MYC expression in cancer. We show that MINCR is functional and controls cell cycle progression by influencing the expression of MYC-regulated cell cycle genes. MINCR is, therefore, a novel player in MYC's transcriptional network, with the potential to open new therapeutic windows in the fight against malignant lymphoma and, possibly, all cancers that rely on MYC expression.

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Burkitt's lymphoma

Cited by 526 publications

References 136 publications

Tuberous sclerosis complex is required for tumor maintenance in MYC‐driven Burkitt's lymphoma

Tuberous sclerosis complex is required for tumor maintenance in MYC‐driven Burkitt's lymphoma

The NADPH Oxidase Inhibitor Imipramine-Blue in the Treatment of Burkitt Lymphoma

MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

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