loading...| Preferred Name | Diffuse Large-B-Cell Lymphoma | |
| Synonyms |
PathwayType: signaling CellType: cancer cell PMID: 19642739 CellType: B-cell Organ_System: lymphatic system Description: Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large transformed B cells and accounts for 30-40? of all adult non-Hodgkin lymphomas, making it the most common type. Pathway is built manually using published studies. PMID: 22224767 PMID: 20393178 PMID: 19577170 Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-7831e948-099a-4ee0-a4a0-baccd7c42891 Notes: Headnote: Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large transformed B-cells and accounts for 30-40% of all adult non-Hodgkin lymphomas, making it the most common type. DLBCL is subdivided into many categories based on biological properties and localization.Gene-expression profiling divides DLBCL into three histologically indistinguishable molecular subtypes: activated B-cell-like (ABC) DLBCL, germinal center B-cell-like (GCB) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). The process of malignant transformation differs for each subtype and the three subtypes vary in clinical presentation and cure rates. Signaling description: ABC DLBCLs characteristically express several genes that are normally expressed in plasma cells. The pathogenetic hallmark of ABC DLBCL is the constitutive activation of the NF-kB signaling pathway due to mutations/deletions of TNFAIP3 and activating mutations in NFKBIZ, MYD88, and CARD11. About 20% of ABC lymphomas have mutations in CD79A or CD79B leading to chronic active B-cell receptor signaling. ABC DLBCLs are characterized by amplifications and consecutive overexpression of BCL2 as well as deletions affecting CDKN2A and CDKN2B. ABC DLBCL has an unfavorable prognosis and remains the least curable form of this malignancy despite recent advances in therapy. GCB DLBCL has an expression profile typical for germinal center cells and does not seem to be influenced by NF-kB signaling. A significant fraction of GCB DLBCL cases have a t(14;18) (q32; q21) activating BCL2. In addition, PTEN deletions and PTEN suppression by miR-17-92 microRNA (miRNA) cluster leads to the constitutive activation of PI3K/Akt signaling. GCB DLBCLs are characterized by activating mutations of MDM2 and BCL-6 and inactivating mutations of TP53, CREBBP, EP300, and ING1. GCB DLBCL has a more favorable prognosis compared to ABC DLBCL. PMBL is characterized by the constitutive activation of NF-kB signaling resulting from TNFAIP3 and REL mutations. The gain or amplification of JAK2 and deletion of SOCS1 contribute to continuous JAK2/STAT signaling. CIITA translocations or CD274 and PDCD1LG2 activating mutations lead to the suppression of antitumor T-cell response. The role of Epstein Barr Virus (EBV) in DLBCL is restricted to a rare subset called Epstein Barr Virus-Positive Diffuse Large B-cell Lymphoma of the Elderly. EBV proteins such as LMP1, LMP-2A, and EBNA-1 play a major role in its pathogenesis. Furthermore, anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL) is another rare subtype which is characterized by translocations t(2;17)(p23;q23) and t(2;5)(p23;q35) leading to CLTC-ALK and NPM-ALK fusion protein formation, respectively. In addition, intravascular large B-cell lymphoma (IVLBCL) is a rare type of large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of small blood vessels, particularly capillaries, but not larger arteries and veins due to the lack of ITGB1 and ICAM-1 expression, which are molecules important for transvascular lymphocyte migration. The combination of chemotherapeutic agents (vincristine, cytoxan, doxorubicin, and prednisolone) and anti-CD20 antibodies (rituximab) can cure approximately 505 of DLBCL cases. Outcome effects: In conclusion, the resulting signaling inhibits plasma cell differentiation and leads to increased proliferation and block of apoptosis. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. Viral proteins are shown in grey. Mutated genes: Mutated genes are shown in white-out style. NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 22409819 PMID: 20582737 Organ: lymph node Source: Diseases |
|
| ID |
urn:agi-pathway:uuid-7831e948-099a-4ee0-a4a0-baccd7c42891 |
|
| database_cross_reference |
PS:PathwayType PS:Description PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
|
| has_exact_synonym |
PathwayType: signaling CellType: cancer cell PMID: 19642739 CellType: B-cell Organ_System: lymphatic system Description: Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large transformed B cells and accounts for 30-40? of all adult non-Hodgkin lymphomas, making it the most common type. Pathway is built manually using published studies. PMID: 22224767 PMID: 20393178 PMID: 19577170 Notes: Headnote: Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large transformed B-cells and accounts for 30-40% of all adult non-Hodgkin lymphomas, making it the most common type. DLBCL is subdivided into many categories based on biological properties and localization.Gene-expression profiling divides DLBCL into three histologically indistinguishable molecular subtypes: activated B-cell-like (ABC) DLBCL, germinal center B-cell-like (GCB) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). The process of malignant transformation differs for each subtype and the three subtypes vary in clinical presentation and cure rates. Signaling description: ABC DLBCLs characteristically express several genes that are normally expressed in plasma cells. The pathogenetic hallmark of ABC DLBCL is the constitutive activation of the NF-kB signaling pathway due to mutations/deletions of TNFAIP3 and activating mutations in NFKBIZ, MYD88, and CARD11. About 20% of ABC lymphomas have mutations in CD79A or CD79B leading to chronic active B-cell receptor signaling. ABC DLBCLs are characterized by amplifications and consecutive overexpression of BCL2 as well as deletions affecting CDKN2A and CDKN2B. ABC DLBCL has an unfavorable prognosis and remains the least curable form of this malignancy despite recent advances in therapy. GCB DLBCL has an expression profile typical for germinal center cells and does not seem to be influenced by NF-kB signaling. A significant fraction of GCB DLBCL cases have a t(14;18) (q32; q21) activating BCL2. In addition, PTEN deletions and PTEN suppression by miR-17-92 microRNA (miRNA) cluster leads to the constitutive activation of PI3K/Akt signaling. GCB DLBCLs are characterized by activating mutations of MDM2 and BCL-6 and inactivating mutations of TP53, CREBBP, EP300, and ING1. GCB DLBCL has a more favorable prognosis compared to ABC DLBCL. PMBL is characterized by the constitutive activation of NF-kB signaling resulting from TNFAIP3 and REL mutations. The gain or amplification of JAK2 and deletion of SOCS1 contribute to continuous JAK2/STAT signaling. CIITA translocations or CD274 and PDCD1LG2 activating mutations lead to the suppression of antitumor T-cell response. The role of Epstein Barr Virus (EBV) in DLBCL is restricted to a rare subset called Epstein Barr Virus-Positive Diffuse Large B-cell Lymphoma of the Elderly. EBV proteins such as LMP1, LMP-2A, and EBNA-1 play a major role in its pathogenesis. Furthermore, anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL) is another rare subtype which is characterized by translocations t(2;17)(p23;q23) and t(2;5)(p23;q35) leading to CLTC-ALK and NPM-ALK fusion protein formation, respectively. In addition, intravascular large B-cell lymphoma (IVLBCL) is a rare type of large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of small blood vessels, particularly capillaries, but not larger arteries and veins due to the lack of ITGB1 and ICAM-1 expression, which are molecules important for transvascular lymphocyte migration. The combination of chemotherapeutic agents (vincristine, cytoxan, doxorubicin, and prednisolone) and anti-CD20 antibodies (rituximab) can cure approximately 505 of DLBCL cases. Outcome effects: In conclusion, the resulting signaling inhibits plasma cell differentiation and leads to increased proliferation and block of apoptosis. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. Viral proteins are shown in grey. Mutated genes: Mutated genes are shown in white-out style. NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 22409819 PMID: 20582737 Organ: lymph node Source: Diseases |
|
| id |
urn:agi-pathway:uuid-7831e948-099a-4ee0-a4a0-baccd7c42891 |
|
| label |
Diffuse Large-B-Cell Lymphoma |
|
| notation |
uuid-7831e948-099a-4ee0-a4a0-baccd7c42891 |
|
| prefLabel |
Diffuse Large-B-Cell Lymphoma |
|
| treeView |
urn:agi-folder:d urn:agi-folder:diffuse_large-b-cell_lymphoma urn:agi-folder:lymphatic_system |
|
| subClassOf |
urn:agi-folder:d urn:agi-folder:diffuse_large-b-cell_lymphoma urn:agi-folder:lymphatic_system |