Role of MYC in B Cell Lymphomagenesis

Korać, Petra; Dotlić, Snježana; Matulić, Maja; Petranović, Matea Zajc; Dominis, Mara

doi:10.3390/genes8040115

Cited by 27 publications

(21 citation statements)

References 118 publications

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“…Proto-oncoprotein c-Myc (hereafter Myc) is a master nuclear factor associated with cell proliferation, survival, and apoptosis [ 1 ]. Overexpression of Myc features numerous malignancies that include the highly aggressive B-cell lymphomas, such as Burkitt’s lymphomas, and also a subset of diffuse large B-cell lymphomas (DLBCL) [ 2 , 3 ]. Myc plays a central role in a large variety of malignancies, and therefore strategies aimed at targeting Myc have emerged as attractive cancer treatments.…”

Section: Introductionmentioning

confidence: 99%

Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis

et al. 2017

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Hyper activity of protooncogene c-Myc is one of the hallmarks of highly aggressive lymphomas. However, the mechanism of how c-Myc is subjected to activation and amplification is still not well defined. In this study, we use gene knockout strategy to show that targeted depletion of a well-conserved microRNA gene locus miR-144/451 initiates tumorigenesis including B-lymphoma development in aged mice. This is due, at least in part, to the direct activation of the c-Myc gene by loss of miR-144/451 expression in hematopoietic cells. Moreover, oncoprotein c-Myc inversely regulates miR-144/451 expression by directly binding to the miR-144/451 promoter region, forming a miRNA-Myc positive feedback loop to safeguard the high level of c-Myc in B-lymphocytes. We also demonstrate that this miRNA-Myc crosstalk is disrupted in human diffuse large B-cell lymphomas with aberrant c-Myc expression. Therefore, our findings provide strong evidence, for the first time, that deficiency of miR-144/451 expression may play a bona fide role in derepression of silenced c-Myc, which contributes to tumor development including B-lymphomagenesis.

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Section: Introductionmentioning

confidence: 99%

Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis

et al. 2017

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“…In BL, high level of MYC and founder alterations induce a field defect characterized by the aberrant activation of PI3K signaling pathway and other changes mediated by the non-canonical binding of MYC to other proteins and genetic loci [ 29 , 53 , 54 ]. A constitutive and disregulated early expression of MYC and the synergism between MYC and the MYC-related miRNAs can overcome the transcriptional program mediated by BCL6.…”

Section: Discussionmentioning

confidence: 99%

MYC-related microRNAs signatures in non-Hodgkin B-cell lymphomas and their relationships with core cellular pathways

et al. 2018

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In order to investigate the role of microRNAs in the pathogenesis of different B-cell lymhoma subtypes, we have applied an array-based assay to a series of 76 mixed non-Hodgkin B-cell lymphomas, including Burkitt’s lymphoma (BL), diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, mantle cell lymphoma (MCL) and follicular lymphoma. Lymphomas clustered according to histological subtypes, driven by two miRNA clusters (the miR-29 family and the miR-17-92 cluster). Since the two miRNA clusters are known to be MYC-regulated, we investigated whether this would be supported in MYC-driven experimental models, and found that this signature separated BL cell lines and a MYC-translocated MCL cell lines from normal germinal center B-cells and other B-cell populations. Similar results were also reproduced in tissue samples comparing BL and reactive lymph node samples. The same series was then quantitatively analyzed for MYC expression by immunohistochemistry and MYC protein levels were compared with corresponding miRNA signatures. A specific metric was developed to summarize the levels of MYC-related microRNAs and the corresponding protein levels. We found that MYC-related signatures are directly related to MYC protein expression across the whole spectrum of B-cells and B-cell lymphoma, suggesting that the MYC-responsive machinery shows predominantly quantitative, rather than qualitative, modifications in B-cell lymphoma. Novel MYC-related miRNAs were also discovered by this approach. Finally, network analysis found that in BL MYC-related differentially expressed miRNAs could control, either positively or negatively, a limited number of hub proteins, including BCL2, CDK6, MYB, ZEB1, CTNNB1, BAX and XBP1.

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“…MYC is re-expressed after (antigen) activation of the BCR, promoting proliferation and inhibiting differentiation of mature B cells [ 39 , 40 ]. After positive selection, MYC expression is downregulated, allowing B cells to differentiate into memory B cells or plasmablasts and to exit the germinal center [ 39 , 41 ]. In plasmablasts, MYC expression is suppressed, allowing terminal B cell differentiation into plasma cells [ 42 ].…”

Section: The Role Of Myc In Normal B Cell Developmentmentioning

confidence: 99%

Impact of MYC on Anti-Tumor Immune Responses in Aggressive B Cell Non-Hodgkin Lymphomas: Consequences for Cancer Immunotherapy

Jonge

Mutis

Roemer

et al. 2020

Cancers

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Patients with MYC overexpressing high grade B cell lymphoma (HGBL) face significant dismal prognosis after treatment with standard immunochemotherapy regimens. Recent preclinical studies indicate that MYC not only contributes to tumorigenesis by its effects on cell proliferation and differentiation, but also plays an important role in promoting escape from anti-tumor immune responses. This is of specific interest, since reversing tumor immune inhibition with immunotherapy has shown promising results in the treatment of both solid tumors and hematological malignancies. In this review, we outline the current understanding of impaired immune responses in B cell lymphoid malignancies with MYC overexpression, with a particular emphasis on diffuse large B cell lymphoma. We also discuss clinical consequences of MYC overexpression in the treatment of HGBL with novel immunotherapeutic agents and potential future treatment strategies.

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Role of MYC in B Cell Lymphomagenesis

Cited by 27 publications

References 118 publications

Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis

Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis

MYC-related microRNAs signatures in non-Hodgkin B-cell lymphomas and their relationships with core cellular pathways

Impact of MYC on Anti-Tumor Immune Responses in Aggressive B Cell Non-Hodgkin Lymphomas: Consequences for Cancer Immunotherapy

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