loading...| Preferred Name |
Follicular Lymphoma |
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| Synonyms |
PathwayType: signaling CellType: cancer cell PMID: 17039231 CellType: B-cell Organ_System: lymphatic system Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-fea803fe-56c1-460e-a850-5f3f9b2327fd PMID: 22973275 PMID: 22224767 PMID: 21970951 PMID: 23023713 PMID: 21083019 Description: Follicular lymphoma is the second most common type of non-Hodgkin lymphoma. Pathway is built manually using published studies. Notes: Headnote: Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and it occurs at an average age of 60 years. It is indolent and characterized by slow progression with a high response to therapy. Nonetheless, most patients eventually develop increasingly resistant disease, and in up to 45% of cases, the original indolent lymphoma transforms into an aggressive subtype. FL generally involves the lymph nodes (LN), spleen, bone marrow (BM), and peripheral blood. The majority of patients present with stage III/IV disease at the time of diagnosis. Morphologically, FL is defined as a mature B-cell neoplasm resulting from the malignant transformation of germinal center derived follicular B-cells. Neoplastic cells are organized in follicles. FL is subdivided into grades 1, 2, 3a, and 3b based on morphology criteria (number of centroblasts); grade 1 has the most favorable prognosis while grade 3b is the most aggressive. Signaling description: Over 85% of FL cases display t(14;18) translocation which results in IGH/BCL2 fusion formation and constant BCL2 activation. The current (Hypothesis) of FL pathogenesis recognizes t(14;18)-positive circulating B-cells as potentially tumor-initiating cells but it is challenged by the observation that similar cells can be detected in the blood of 50-70% of healthy individuals who are not prone to developing FL. Additional oncogenic events are clearly required for full malignant transformation. They include genetic and epigenetic changes. Genetic changes are represented by TNFRSF14, TNFAIP3, EPHA7, and histone-modifying genes (EZH2, MLL2, CREBBP, EP300, and MEF2B) mutations. Epigenetic changes include aberrant methylation of the CDKN2A, CDKN2B, CDKN1C, GSTP1, PLK2, PTPN6, DAPK1, GADD45G, IL12RB2, and androgen receptor (AR) genes. In addition, the transformation of FL into aggressive lymphomas occurs due to MYC and BCL-6 activating mutations as well as TP53, ATM, CDKN2A, CDKN2B, and FAS deletions or inactivating mutations. Furthermore, microenvironment plays an important role in FL development. Beneficial signals for growth and survival include IL-4, IL-21, CXCL12, and CXCL13. B-cell receptor (BCR) signaling occurs through the stimulation of BCR by the innate immune system through N-glycans or by specific antigen presentation. T-helper cells interact with FL cells through their T-cell receptor, MHC class II and CD40L/CD40, providing survival signals. In conclusion, as any indolent lymphoma, FL in early stages has a good response to standard chemotherapy (includes Cytoxan, vincristine, doxorubicin, prednisolone) plus anti-CD20 antibodies (rituximab). The median overall survival time reaches 10 years or more with current treatment. Outcome effects: Overall, the genetic changes in FL result in block of apoptosis and /or activation of proliferation and inhibit plasma cell differentiation. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. Mutated genes: Mutated genes are shown in white-out style. NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 12959350 Organ: lymph node Source: Diseases |
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| ID |
urn:agi-pathway:uuid-fea803fe-56c1-460e-a850-5f3f9b2327fd |
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| 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 |
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| has_exact_synonym |
PathwayType: signaling CellType: cancer cell PMID: 17039231 CellType: B-cell Organ_System: lymphatic system PMID: 22973275 PMID: 22224767 PMID: 21970951 PMID: 23023713 PMID: 21083019 Description: Follicular lymphoma is the second most common type of non-Hodgkin lymphoma. Pathway is built manually using published studies. Notes: Headnote: Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and it occurs at an average age of 60 years. It is indolent and characterized by slow progression with a high response to therapy. Nonetheless, most patients eventually develop increasingly resistant disease, and in up to 45% of cases, the original indolent lymphoma transforms into an aggressive subtype. FL generally involves the lymph nodes (LN), spleen, bone marrow (BM), and peripheral blood. The majority of patients present with stage III/IV disease at the time of diagnosis. Morphologically, FL is defined as a mature B-cell neoplasm resulting from the malignant transformation of germinal center derived follicular B-cells. Neoplastic cells are organized in follicles. FL is subdivided into grades 1, 2, 3a, and 3b based on morphology criteria (number of centroblasts); grade 1 has the most favorable prognosis while grade 3b is the most aggressive. Signaling description: Over 85% of FL cases display t(14;18) translocation which results in IGH/BCL2 fusion formation and constant BCL2 activation. The current (Hypothesis) of FL pathogenesis recognizes t(14;18)-positive circulating B-cells as potentially tumor-initiating cells but it is challenged by the observation that similar cells can be detected in the blood of 50-70% of healthy individuals who are not prone to developing FL. Additional oncogenic events are clearly required for full malignant transformation. They include genetic and epigenetic changes. Genetic changes are represented by TNFRSF14, TNFAIP3, EPHA7, and histone-modifying genes (EZH2, MLL2, CREBBP, EP300, and MEF2B) mutations. Epigenetic changes include aberrant methylation of the CDKN2A, CDKN2B, CDKN1C, GSTP1, PLK2, PTPN6, DAPK1, GADD45G, IL12RB2, and androgen receptor (AR) genes. In addition, the transformation of FL into aggressive lymphomas occurs due to MYC and BCL-6 activating mutations as well as TP53, ATM, CDKN2A, CDKN2B, and FAS deletions or inactivating mutations. Furthermore, microenvironment plays an important role in FL development. Beneficial signals for growth and survival include IL-4, IL-21, CXCL12, and CXCL13. B-cell receptor (BCR) signaling occurs through the stimulation of BCR by the innate immune system through N-glycans or by specific antigen presentation. T-helper cells interact with FL cells through their T-cell receptor, MHC class II and CD40L/CD40, providing survival signals. In conclusion, as any indolent lymphoma, FL in early stages has a good response to standard chemotherapy (includes Cytoxan, vincristine, doxorubicin, prednisolone) plus anti-CD20 antibodies (rituximab). The median overall survival time reaches 10 years or more with current treatment. Outcome effects: Overall, the genetic changes in FL result in block of apoptosis and /or activation of proliferation and inhibit plasma cell differentiation. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. Mutated genes: Mutated genes are shown in white-out style. NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 12959350 Organ: lymph node Source: Diseases |
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| id |
urn:agi-pathway:uuid-fea803fe-56c1-460e-a850-5f3f9b2327fd |
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| label |
Follicular Lymphoma |
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| notation |
uuid-fea803fe-56c1-460e-a850-5f3f9b2327fd |
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| prefLabel |
Follicular Lymphoma |
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| treeView |
urn:agi-folder:f urn:agi-folder:follicular_lymphoma urn:agi-folder:lymphatic_system |
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| subClassOf |
urn:agi-folder:f urn:agi-folder:follicular_lymphoma urn:agi-folder:lymphatic_system |