Taken together, MALT1 protease maintained mitochondrial redox homeostasis and mitochondrial bioenergetics through the MALT1-c-Jun-GLS1-coupled metabolic pathway to defend against apoptosis in ABC-DLBCL cells, which raises exciting possibilities regarding targeting of the MALT1-c-Jun-GLS1 axis as a potential therapeutic strategy against ABC-DLBCL.
Moreover, constitutive MALT1 phosphorylation promotes survival of activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) cells addicted to chronic BCR signaling.
Autocleavage of the paracaspaseMALT1 at Arg-781 attenuates NF-κB signaling and regulates the growth of activated B-cell like diffuse large B-cell lymphoma cells.
The paracaspaseMALT1 plays an essential role in activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) downstream of B cell and TLR pathway genes mutated in these tumors.
Therefore, we assessed here the simultaneous inhibition of BTK and the protease MALT1 that acts downstream of CARMA1 and is essential for ABC DLBCL tumor growth.
In conclusion, these results provide novel clinical and biological insight into the tumor-suppressive role of PRDM1/BLIMP-1 in ABC-DLBCL patients and suggest that loss of PRDM1/BLIMP-1 function contributes to the overall poor prognosis of ABC-DLBCL patients.
Here, we show that N-terminal misfolding mutations in ABC-DLBCL render Blimp-1 protein susceptible to proteasome-mediated degradation but spare its transcription-regulating activity.
We report here that the BLIMP1 gene is inactivated by structural alterations in 24% (8 out of 34) activated B cell-like diffuse large cell lymphoma (ABC-DLBCL), but not in GC B cell-like (n = 0/37) or unclassified (n = 0/21) DLBCL.
Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-<i>κ</i>B p65, Syk, Bruton's tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients.
Recent work further demonstrated that this noncanonical mechanism is conserved with JAK1, which is activated by the autocrine cytokines IL6 and IL10 in activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL), a cancer type that is particularly difficult to treat and has poor prognosis.
By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphomalacks the N-terminal 100 amino acids of full-length FOXP1.
In this study, immunohistochemical analysis of 31 tumor tissues from DLBCL patients [20 of ABC subtype and 11 of germinal center B-cell-like (GCB) subtype] and 11 normal lymph nodes revealed that HO-1 overexpression was characteristic of ABC-DLBCL.
Here we prove by mass spectrometry and N-terminal antibody staining that FOXP1S proteins in activated B-cell-like diffuse large B-cell lymphoma are N-terminally truncated.
The isolated MYC+/BCL6+/BCL2- subset, more frequent in germinal center B-cell like diffuse large B-cell lymphoma, had significantly better survival compared with the isolated MYC+/BCL2+/BCL6- subset (more frequent in activated B-cell like diffuse large B-cell lymphoma).
Cell-line derived FOXP1 target genes that were highly correlated with FOXP1 expression in primary DLBCL accurately segregated the corresponding clinical subtypes of a large cohort of primary DLBCL isolates and identified conserved pathways associated with ABC-DLBCL pathology.
Contrary to most cutaneous lymphomas that rarely harbor primary genetic alteration of their nodal histological equivalent, primary cutaneous large B-cell lymphoma, leg type seems to be a 'cutaneous counterpart' of activated B-cell-like diffuse large B-cell lymphoma with a similar cytogenetic profile and a high rate of MYD88 oncogenic L265P mutation.
In a population-based patient cohort, SPIBhigh/BATFlow-ABC-DLBCL is enriched for mutation of MYD88, and SPIBhigh/BATFlow-ABC-DLBCL with MYD88-L265P mutation identifies a small subgroup of patients among this otherwise aggressive disease subgroup with distinct favourable outcome.
Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours.
BCL2 protein expression has significant impact on overall survival (OS) and event-free survival (EFS) in DLBCL (OS, P = 0.009; EFS, P = 0.001) and GCB-DLBCL (OS, P = 0.03; EFS, P = 0.002) but not in ABC-DLBCL in the R-CHOP cohort.
In this study, we have compared by means of RNAscope technology STAT3 RNA expression in human DLBCL in a selected group of activated B-cell-like DLBCL (ABC-DLBCL) patients with another group of germinal center B-cell-like DLBCL (GBC-DLBCL) patients.
In conclusion, these data show that p50 is important as a unique mechanism of R-CHOP-resistance in activated B-cell-like diffuse large B-cell lymphoma and in patients without TP53 mutations.
Therefore, we assessed here the simultaneous inhibition of BTK and the protease MALT1 that acts downstream of CARMA1 and is essential for ABC DLBCL tumor growth.