loading...| Preferred Name | Hodgkin Lymphoma | |
| Synonyms |
PathwayType: signaling CellType: cancer cell Organ_System: lymphatic system Description: Classical HL is characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells, which are transformed post-germinal center B-cells. Pathway is built manually using published studies. PMID: 22224767 PMID: 23023715 PMID: 16304386 PMID: 19078975 PMID: 20008234 NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 15086409 CellType: Reed Sternberg cell Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-037e2c70-b0f5-470b-aa15-d86985cf0301 Organ: lymph node Source: Diseases PMID: 14700604 Notes: Headnote: Hodgkin lymphoma (HL) is one of the most frequent types of lymphoma in the Western world. The main clinical presentation is lymph node enlargement. It is subdivided into classical HL and nodular lymphocyte-predominant HL (NLPHL which accounts for only 5% of cases). Classical HL, based on histological features, is further subdivided into 4 groups: 1) nodular sclerosis, 2) mixed cellularity HL, 3) lymphocyte depletion HL and 4) lymphocyte-rich HL. Nodular sclerosis HL accounts for about 60% of cases. Signaling description: Classical HL is characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells, which are transformed post-germinal center B-cells destined for apoptosis since they have not undergone successful immunoglobulin gene rearrangement. Several mechanisms which are not clearly understood allow these cells to survive. HRS cells account for only about 1% of cells in the tumor tissue. The majority of cells in HL lesions are a mixed infiltrate of various types of cells of the immune system (T-cells, neutrophils, eosinophils, mast cells, and others). This microenvironment promotes the survival of HRS cells and helps them escape attack from cytotoxic T or natural killer (NK) cells. Classical HL is unique among human lymphomas in the extent to which the lymphoma cells have undergone reprogramming of gene expression. They have lost expression of most B cell-typical genes (B cell receptor (BCR), immunoglobulins, and many B-cell specific CD markers) and acquired expression of multiple genes typical for T-cells, myeloid cells, mast cells, and dendritic cells.Multiple signaling pathways and transcription factors show deregulated activity in HRS cells: NF-kB, JAK-STAT, PI3K/Akt, RAS-MAPK, NOTCH 1 and receptor tyrosine kinases. HRS cells also show constitutive activity of both the classical (canonical) and alternative (or non-canonical) NF-kB signaling pathways, which is regarded as the major pathogenetic mechanism in HL.NF-kB activity in HRS cells is mediated by diverse mechanisms: receptor signaling through CD40, TNFRSF8 (CD30), TNFRSF11A (RANK), TNFRSF17 (BCMA), and TNFRSF13B (TACI), genomic REL amplification, inactivating mutations in NFKBIA and NFKBIE, and signaling through the EBV protein LMP1. EBV is found in HRS cells in about 40% of classical HL. In pediatric HL, this association can be up to 90% and HL in patients with AIDS show EBV-infected HRS cells in nearly all cases. EBV proteins such as LMP1, LMP2A, and EBNA1 play a role in the pathophysiology of HL. LMP1 mimics an active CD40 receptor, thereby inducing constitutive NF-kB activation and can also activate JUN/FOS, PI3K, and JAK/STAT signaling. LMP2A can replace the function of an active BCR and mimic BCR signaling. EBNA1 blocks SMAD2, thereby interrupting TGF-beta receptor (TGFBR) signaling and decreasing the level of PTPRK, a member of the protein tyrosine phosphatase (PTP) family. The role of EBV in HL is important, but facultative, as 60% of patients develop the disease without EBV. In conclusion, the treatment of HL has been proven to be successful with the current treatment protocols involving multi-agent chemotherapy and/or radiotherapy (bleomycin, etoposide, Cytoxan, vincristine, procarbazine, and prednisone) and achieve cure rates of 80-90%. Outcome effects: The down-regulation of B-cell commitment genes such as PAX-5, EBF-1, and TCF-3 is responsible for the expression of myeloid and T-cell markers and loss of expression of most B-cell markers. In addition, the down-regulation of POU2AF1, POU2F2, and SPI1 genes is responsible for the block of immunoglobulins synthesis. Prominent lymph node fibrosis is a typical feature of most types of HL and originates from HRS cell-mediated fibroblast activation. Highlighted proteins: Viral proteins are shown in grey. Mutated genes: Mutated genes are shown in white-out style. |
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urn:agi-pathway:uuid-037e2c70-b0f5-470b-aa15-d86985cf0301 |
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PS:PathwayType PS:Description PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PathwayType: signaling CellType: cancer cell Organ_System: lymphatic system Description: Classical HL is characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells, which are transformed post-germinal center B-cells. Pathway is built manually using published studies. PMID: 22224767 PMID: 23023715 PMID: 16304386 PMID: 19078975 PMID: 20008234 NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 15086409 CellType: Reed Sternberg cell Organ: lymph node Source: Diseases PMID: 14700604 Notes: Headnote: Hodgkin lymphoma (HL) is one of the most frequent types of lymphoma in the Western world. The main clinical presentation is lymph node enlargement. It is subdivided into classical HL and nodular lymphocyte-predominant HL (NLPHL which accounts for only 5% of cases). Classical HL, based on histological features, is further subdivided into 4 groups: 1) nodular sclerosis, 2) mixed cellularity HL, 3) lymphocyte depletion HL and 4) lymphocyte-rich HL. Nodular sclerosis HL accounts for about 60% of cases. Signaling description: Classical HL is characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells, which are transformed post-germinal center B-cells destined for apoptosis since they have not undergone successful immunoglobulin gene rearrangement. Several mechanisms which are not clearly understood allow these cells to survive. HRS cells account for only about 1% of cells in the tumor tissue. The majority of cells in HL lesions are a mixed infiltrate of various types of cells of the immune system (T-cells, neutrophils, eosinophils, mast cells, and others). This microenvironment promotes the survival of HRS cells and helps them escape attack from cytotoxic T or natural killer (NK) cells. Classical HL is unique among human lymphomas in the extent to which the lymphoma cells have undergone reprogramming of gene expression. They have lost expression of most B cell-typical genes (B cell receptor (BCR), immunoglobulins, and many B-cell specific CD markers) and acquired expression of multiple genes typical for T-cells, myeloid cells, mast cells, and dendritic cells.Multiple signaling pathways and transcription factors show deregulated activity in HRS cells: NF-kB, JAK-STAT, PI3K/Akt, RAS-MAPK, NOTCH 1 and receptor tyrosine kinases. HRS cells also show constitutive activity of both the classical (canonical) and alternative (or non-canonical) NF-kB signaling pathways, which is regarded as the major pathogenetic mechanism in HL.NF-kB activity in HRS cells is mediated by diverse mechanisms: receptor signaling through CD40, TNFRSF8 (CD30), TNFRSF11A (RANK), TNFRSF17 (BCMA), and TNFRSF13B (TACI), genomic REL amplification, inactivating mutations in NFKBIA and NFKBIE, and signaling through the EBV protein LMP1. EBV is found in HRS cells in about 40% of classical HL. In pediatric HL, this association can be up to 90% and HL in patients with AIDS show EBV-infected HRS cells in nearly all cases. EBV proteins such as LMP1, LMP2A, and EBNA1 play a role in the pathophysiology of HL. LMP1 mimics an active CD40 receptor, thereby inducing constitutive NF-kB activation and can also activate JUN/FOS, PI3K, and JAK/STAT signaling. LMP2A can replace the function of an active BCR and mimic BCR signaling. EBNA1 blocks SMAD2, thereby interrupting TGF-beta receptor (TGFBR) signaling and decreasing the level of PTPRK, a member of the protein tyrosine phosphatase (PTP) family. The role of EBV in HL is important, but facultative, as 60% of patients develop the disease without EBV. In conclusion, the treatment of HL has been proven to be successful with the current treatment protocols involving multi-agent chemotherapy and/or radiotherapy (bleomycin, etoposide, Cytoxan, vincristine, procarbazine, and prednisone) and achieve cure rates of 80-90%. Outcome effects: The down-regulation of B-cell commitment genes such as PAX-5, EBF-1, and TCF-3 is responsible for the expression of myeloid and T-cell markers and loss of expression of most B-cell markers. In addition, the down-regulation of POU2AF1, POU2F2, and SPI1 genes is responsible for the block of immunoglobulins synthesis. Prominent lymph node fibrosis is a typical feature of most types of HL and originates from HRS cell-mediated fibroblast activation. Highlighted proteins: Viral proteins are shown in grey. Mutated genes: Mutated genes are shown in white-out style. |
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| id |
urn:agi-pathway:uuid-037e2c70-b0f5-470b-aa15-d86985cf0301 |
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| label |
Hodgkin Lymphoma |
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| notation |
uuid-037e2c70-b0f5-470b-aa15-d86985cf0301 |
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| prefLabel |
Hodgkin Lymphoma |
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| treeView |
urn:agi-folder:h urn:agi-folder:lymphatic_system urn:agi-folder:hodgkin_lymphoma |
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urn:agi-folder:h urn:agi-folder:lymphatic_system urn:agi-folder:hodgkin_lymphoma |