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IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
IFITM3 shifts upon phosphorylation from acting as an antiviral effector to being a scaffold for PIP3 and thereby amplifies PI3K signalling, which can be co-opted for malignant transformation in B cell leukaemia and lymphoma.
- Jaewoong Lee
- , Mark E. Robinson
- & Markus Müschen
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Letter |
A multiprotein supercomplex controlling oncogenic signalling in lymphoma
A pro-survival multiprotein signalling supercomplex consisting of the B cell receptor, MYD88, TLR9 and mTOR is discovered that coordinates NF-κB activation in diffuse large B cell lymphoma, and provides mechanistic insight into the efficacy of drug combinations.
- James D. Phelan
- , Ryan M. Young
- & Louis M. Staudt
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Letter |
Senescence-associated reprogramming promotes cancer stemness
Cellular senescence induced by chemotherapy leads to the acquisition of stemness in cancer cells, which results in enhanced tumour-promoting capacity after forced release or spontaneous escape from the senescent cell-cycle arrest.
- Maja Milanovic
- , Dorothy N. Y. Fan
- & Clemens A. Schmitt
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Letter |
The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition
Combined studies in MYC-driven mouse lymphomas and human Burkitt lymphoma unravel an essential role for the B-cell antigen receptor in the control of tumour B-cell fitness both in vitro and in vivo, with possible biological and clinical implications.
- Gabriele Varano
- , Simon Raffel
- & Stefano Casola
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Letter |
Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens
Evidence for the abundant presentation of class II neoantigens by a human B-cell lymphoma.
- Michael S. Khodadoust
- , Niclas Olsson
- & Ash A. Alizadeh
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Letter |
Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma
Inactivation of the S1PR2–Gα13–ARHGEF1 signalling pathway in mice allows Akt activation and promotes dissemination of germinal centre B cells, consistent with a role of function-disrupting mutations in the systemic dissemination of diffuse large B-cell lymphoma.
- Jagan R. Muppidi
- , Roland Schmitz
- & Jason G. Cyster
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Letter |
Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis
Global transcriptional and epigenomic analyses in diverse cell types reveal that the primary action of Myc is to up- and downregulate transcription of distinct groups of genes, rather than to amplify transcription of all active genes; general RNA amplification, when observed, is better explained as an indirect consequence of Myc’s action on cellular physiology.
- Arianna Sabò
- , Theresia R. Kress
- & Bruno Amati
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Letter |
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy
In mice with Eµ-myc transgenic lymphomas in which therapy-induced senescence (TIS) depends on the H3K9 histone methyltransferase Suv39h1, TIS-competent lymphomas but not TIS-incompetent Suv39h1– lymphomas show increased glucose utilization and ATP production after senescence-inducing chemotherapy to cope with proteotoxic stress elicited by factors of the senescence-associated secretory phenotype (SASP); senescent cancers are selectively vulnerable to drugs that block glucose utilization or autophagy.
- Jan R. Dörr
- , Yong Yu
- & Clemens A. Schmitt
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Letter |
Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics
RNA sequencing of Burkitt lymphoma tumours allows identification of mutations affecting the transcription factor TCF3, its negative regulator ID3 and the cell cycle regulator CCND3; these pathways reveal new targets for potential therapeutic intervention.
- Roland Schmitz
- , Ryan M. Young
- & Louis M. Staudt
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Letter |
FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas
FBXO11 is identified as the F-box protein that normally targets BCL6 for degradation, and FBXO11 deletions or mutations that prevent this function and thus stabilize BCL6 are found in B-cell lymphomas.
- Shanshan Duan
- , Lukas Cermak
- & Michele Pagano
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Article
| Open AccessFrequent mutation of histone-modifying genes in non-Hodgkin lymphoma
- Ryan D. Morin
- , Maria Mendez-Lago
- & Marco A. Marra
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Article |
Inactivating mutations of acetyltransferase genes in B-cell lymphoma
In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.
- Laura Pasqualucci
- , David Dominguez-Sola
- & Riccardo Dalla-Favera
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Letter |
SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction
This is one of two papers demonstrating that in several cancer types including ovarian cancer and T-cell leukaemias, the apoptosis regulator MCL1 is targeted for degradation by the FBW7 tumour suppressor. This study finds that this mechanism can determine the response to drugs targeting BCL2 family apoptosis factors. Deletion or mutation of FBW7 found in cancer patients therefore can render tumours resistant to these therapies.
- Hiroyuki Inuzuka
- , Shavali Shaik
- & Wenyi Wei
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Letter |
Oncogenically active MYD88 mutations in human lymphoma
This study finds frequent mutations in MYD88 in the activated B-cell-like subtype of diffuse large B-cell lymphoma and, with lower frequency, in mucosa-associated lymphoid tissue lymphomas. MYD88 mediates signalling by Toll-like receptors, and the mutations, most of which affect the same amino acid, are shown to activate the pathway and promote cancer cell survival.
- Vu N. Ngo
- , Ryan M. Young
- & Louis M. Staudt
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Research Highlights |
Cancer biology: Cell neighbours aid cancer relapse
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Letter |
OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma
One model for cancer development posits that the proliferating cells in a tumour can become 'addicted' to activating mutations in an oncogene. With the realization that certain microRNAs promote tumorigenesis, it has been proposed that tumours may also become dependent on such 'oncomiRs'. Here, evidence is provided that the gene encoding microRNA-21 is an oncogene, and that in its absence, tumours undergo apoptosis and regress. Thus tumours can indeed become addicted to oncomiRs.
- Pedro P. Medina
- , Mona Nolde
- & Frank J. Slack
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Letter |
Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma
The role of B-cell-receptor (BCR) signalling in human B cell lymphomas has been a long-standing question, with genetic and functional evidence for its oncogenic role in human lymphomas lacking. Here, a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like subtype of diffuse large B-cell lymphoma is described and analysed, with potential implications for future therapeutic strategies.
- R. Eric Davis
- , Vu N. Ngo
- & Louis M. Staudt