Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rare t(X;14)(q28;q32) translocation reveals link between MTCP1 and chronic lymphocytic leukemia

ABSTRACT: Rare, recurrent balanced translocations occur in a variety of cancers but are often not functionally interrogated. Balanced translocations with the immunoglobulin heavy chain locus (IGH; 14q32) in chronic lymphocytic leukemia (CLL) are infrequent but have led to the discovery of pathogenic genes including CCND1, BCL2, and BCL3. Following identification of a t(X;14)(q28;q32) translocation that placed the mature T cell proliferation 1 gene (MTCP1) adjacent to the immunoglobulin locus in a CLL patient, we hypothesized that this gene may have previously unrecognized importance. Indeed, here we report overexpression of human MTCP1 restricted to the B cell compartment in mice produces a clonal CD5+/CD19+ leukemia recapitulating the major characteristics of human CLL and demonstrates favorable response to therapeutic intervention with ibrutinib. We reinforce the importance of genetic interrogation of rare, recurrent balanced translocations to identify cancer driving genes via the story of MTCP1 as a contributor to CLL pathogenesis. Some genes that are part of balanced translocations are reported as drivers for tumourigenesis. Here, the authors report a translocation involving MTCP1 in chronic lymphocytic leukemia and show that MTCP1 overexpression leads to the disease in a murine model.

SUBMITTER: Walker J

PROVIDER: S-EPMC8566464 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Rare germline variants in ATM are associated with chronic lymphocytic leukemia.

Project description: Not available

| S-EPMC5628120 | biostudies-literature

Pericardial Involvement with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Rare Case of Constrictive Pericarditis.

Project description: Not available

| S-EPMC6104145 | biostudies-literature

Bacterial translocation in acute lymphocytic leukemia.

Project description:Bloodstream infection (BSI) is the major cause of mortality in acute lymphocytic leukemia (ALL). Causative pathogens in BSI originate from the gut microbiota due to an increase in intestinal permeability, a process known as bacterial translocation (BT). The gut microbiota in physiological conditions is controlled by a large number of immune cells as part of the gut-associated lymphoid tissue (GALT).The aim of the current study was to investigate the mechanism of bacterial translocation in leukemia by identifying and characterizing alterations in the GALT in leukemic mouse model. Our studies revealed a severe impairment of the GALT characterized by a loss of lymphatic cells in ALL, which eventually led to BSI. We identified differentially expressed genes in the intraepithelium and the lamina propria, which may contribute to BT and to the impairment of lymphocyte migration.

| S-EPMC6443231 | biostudies-literature

Acrocyanosis revealing chronic lymphocytic leukemia.

Project description:Cold agglutinin disease arising in the context of chronic lymphocytic leukemia can misdiagnose a warm autoimmune hemolytic anemia.

| S-EPMC4831394 | biostudies-other

Inflammation, TNFα and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia.

Project description:Patients receiving lenalidomide are at an increased risk for deep venous thrombosis (DVT). Here, we prospectively investigated the DVT risk in patients with relapsed chronic lymphocytic leukemia (CLL) treated with lenalidomide (n = 32). Five patients developed six incidents of DVT over 1 year for an annual incidence of 16%. Three of these were considered drug-related. Median time to DVT was 105 days (range 56-259 days). No pulmonary embolism was detected. Hypercoagulability screen before study entry was negative in all patients who subsequently developed DVTs. Compared to normal volunteers CLL patients had increased baseline levels of D-dimer, thrombin-antithrombin, soluble vascular endothelial adhesion molecule 1 (sVCAM-1), and thrombomodulin (p < 0.001). After 1 week on lenalidomide D-dimer, thrombomodulin, sVCAM-1, factor VIII, TNFα, and C-reactive protein were significantly increased while protein C was decreased (p < 0.001). In patients with lenalidomide-related DVTs, TNFα, and sVCAM-1 were more strongly upregulated than in all other patients (p < 0.05) and TNFα and sVCAM-1 levels were significantly correlated (r = 0.65, p < 0.001). These data link lenalidomide associated DVTs with TNFα upregulation and endothelial cell dysfunction and suggest that aspirin may have a role for DVT prophylaxis in these patients.

| S-EPMC3414537 | biostudies-literature

Familial chronic lymphocytic leukemia.

Project description:Purpose of reviewFamilies with multiple individuals affected with chronic lymphocytic leukemia (CLL) and other related B-cell tumors have been described in the literature and strong familial aggregation has been seen in population studies. However, predisposing germline mutations have not been identified. We will discuss the spectrum of conditions associated with CLL in families and the advances in identifying the underlying susceptibility genes.Recent findingsFamilial CLL does not appear to differ substantially from sporadic CLL in terms of prognostic markers and clinical outcome, although it may be associated with more indolent disease. The precursor condition, monoclonal B-cell lymphocytosis, also aggregates in CLL families. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for susceptibility loci but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated several genes as being important in CLL but more studies are needed. Results from whole-genome association studies are promising.SummaryThe ability to conduct large-scale genomic studies in unrelated CLL patients and in high-risk CLL families will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate causal pathways.

| S-EPMC2891437 | biostudies-literature

Chronic lymphocytic leukemia in China.

Project description: Not available

| S-EPMC9276188 | biostudies-literature

CD73 Promotes Chronic Lymphocytic Leukemia.

Project description:The ecto-nucleotidase CD73 is an important immune checkpoint in tumor immunity that cooperates with CD39 to hydrolyze pro-inflammatory extracellular ATP into immunosuppressive adenosine. While the role of CD73 in immune evasion of solid cancers is well established, its role in leukemia remains unclear. To investigate the role of CD73 in the pathogenesis of chronic lymphocytic leukemia (CLL), Eµ-TCL1 transgenic mice that spontaneously develop CLL were crossed with CD73-/- mice. Disease progression in peripheral blood and spleen, and CLL markers were evaluated by flow cytometry and survival was compared to CD73-proficient Eµ-TCL1 transgenic mice. We observed that CD73 deficiency significantly delayed CLL progression and prolonged survival in Eµ-TCL1 transgenic mice, and was associated with increased accumulation of IFN-γ+ T cells and effector-memory CD8+ T cells. Neutralizing IFN-γ abrogated the survival advantage of CD73-deficient Eµ-TCL1 mice. Intriguingly, the beneficial effects of CD73 deletion were restricted to male mice. In females, CD73 deficiency was uniquely associated with the upregulation of CD39 in normal lymphocytes and sustained high PD-L1 expression on CLL cells. In vitro studies revealed that adenosine signaling via the A2a receptor enhanced PD-L1 expression on Eµ-TCL1-derived CLL cells, and a genomic analysis of human CLL samples found that PD-L1 correlated with adenosine signaling. Our study, thus, identified CD73 as a pro-leukemic immune checkpoint in CLL and uncovered a previously unknown sex bias for the CD73-adenosine pathway.

| S-EPMC9264813 | biostudies-literature

Lenalidomide and chronic lymphocytic leukemia.

Project description:Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS) and tumor flare reaction (TFR), that make its management different from other hematologic malignancies.

| S-EPMC3791640 | biostudies-literature

Regulatory network reconstruction reveals genes with prognostic value for chronic lymphocytic leukemia.

Project description:BackgroundThe clinical course of chronic lymphocytic leukemia (CLL) is highly variable; some patients follow an indolent course, but others progress to a more advanced stage. The mutational status of rearranged immunoglobulin heavy chain variable (IGVH) genes in CLL is a feature that is widely recognized for dividing patients into groups that are related to their prognoses. However, the regulatory programs associated with the IGVH statuses are poorly understood, and markers that can precisely predict survival outcomes have yet to be identified.MethodsIn this study, (i) we reconstructed gene regulatory networks in CLL by applying an information-theoretic approach to the expression profiles of 5 cohorts. (ii) We applied master regulator analysis (MRA) to these networks to identify transcription factors (TFs) that regulate an IGVH mutational status signature. The IGVH mutational status signature was developed by searching for differentially expressed genes between the IGVH mutational statuses in numerous CLL cohorts. (iii) To evaluate the biological implication of the inferred regulators, prognostic values were determined using time to treatment (TTT) and overall survival (OS) in two different cohorts.ResultsA robust IGVH expression signature was obtained, and various TFs emerged as regulators of the signature in most of the reconstructed networks. The TF targets expression profiles exhibited significant differences with respect to survival, which allowed the definition of a reduced profile with a high value for OS. TCF7 and its targets stood out for their roles in progression.ConclusionTFs and their targets, which were obtained merely from inferred regulatory associations, have prognostic implications and reflect a regulatory context for prognosis.

| S-EPMC4659237 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data