Biological Pathway Taxonomy

Last uploaded: March 30, 2022
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Id urn:agi-pathway:uuid-26ce00f6-56f5-4e8c-b1e5-a4d7293b1385
urn:agi-pathway:uuid-26ce00f6-56f5-4e8c-b1e5-a4d7293b1385
Preferred Name

Mantle Cell Lymphoma
Synonyms
PathwayType: signaling
PMID: 19880776
CellType: cancer cell
PMID: 18410453
Notes: Headnote: Mantle cell lymphoma (MCL) represents approximately 4-10% of all cases of non-Hodgkin lymphoma. It occurs primarily among elderly individuals with a median age of approximately 60 years (range 29-85). Most MCL patients have disseminated disease including generalized lymphadenopathies and bone marrow involvement. The clinical behavior of MCL patients is aggressive with a median overall survival of approximately 3-4 years. MCL is a mature B-cell neoplasm arising from antigen-experienced B cells. Signaling description:The genetic hallmark of MCL is the translocation t(11;14)(q13;q32) leading to the formation of a fusion gene and protein, IGH-CCND1 and aberrant expression of cyclin D1 (CCND1) which is not typically expressed in normal lymphocytes. At the same time, several observations suggest that CCND1 dysregulation is not sufficient for cell transformation, nor does it explain the aggressive behavior of MCL. Therefore, secondary chromosome alterations are necessary. MCL has the highest degree of genomic instability among B-cell malignances and many secondary chromosomal alterations of cell-cycle regulation genes have been described in MCL. TP53, RB1, ATM, BCL2L11, SOCS1, CDKN2A, CDKN2C, HIC1, FAF1, TNFAIP3, and CHEK2 genes are frequently inactivated by point mutations or gene deletions. In addition, gene amplifications deregulate additional genes including CDK4, BMI1, MDM2, BCL2, MYC, SYK, and PIK3CA while point mutations may activate NOTCH1. Furthermore, several signaling pathways contribute to MCL pathogenesis including constitutively activated PI3K/AKT1/MTOR, NF-kB, WNT, Hedgehog (SHH), Notch, and JAK/STAT pathways. Further, there are some indications that tumor-host interactions may be more important in MCL than currently believed. It has been shown that IL6, IL10, and CXCL12 may activate JAK/STAT3 pathway. The expression of CD40 and responsiveness to CD40LG suggest that MCL cells can interact with CD40LG-positive T cells. Furthermore, epigenetic changes in MCL are currently under investigation. Several hypomethylated and thereby upregulated genes including NOTCH1, CDK5, and HDAC1 could play a pathogenic role in disease development and progression. MCL is one of the most difficult B-cell lymphomas to treat. Although conventional chemotherapy induces high remission rates in previously untreated patients, relapse within a few years is common contributing to a rather short median survival of 3-4 years. Proteasome inhibitors (bortezomib), MTOR inhibitors (temsirolimus), immunomodulatory drugs (lenalidomide) and new alkylating agents (bendamustine) have recently been added to the treatment options for MCL. Outcome effects: In general, all of the described MCL-related signaling routes promote tumor cell proliferation and survival. The role of CCND1 in MCL lymphomagenesis is related to its function as a regulator of cyclin-dependent kinases, CDK4 and CDK6 during the cell cycle. The binding of CCND1 to CDK4/6 activates the transcription factor, E2F by phosphorylating its inhibitor, RB1, and further promoting cyclin E/CDK2 activation to trigger entry into the S phase of the cell cycle. In addition, the microenvironment most likely plays an important role in the biology of MCL. 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.
CellType: B-cell
Organ_System: lymphatic system
Description: Mantle cell lymphoma (MCL) represents approximately 4-10? of all cases of non-Hodgkin lymphoma. MCL is a mature B-cell neoplasm arising from antigen-experienced B cells. Pathway is built manually using published studies.
PMID: 22224767
PMID: 23023712
PMID: 20940415
Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-26ce00f6-56f5-4e8c-b1e5-a4d7293b1385
NodeType: Pathway
Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin
PMID: 19362399
Organ: lymph node
Source: Diseases
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Type http://www.w3.org/2002/07/owl#Class

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label
Mantle Cell Lymphoma
prefLabel
Mantle Cell Lymphoma
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
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notation
uuid-26ce00f6-56f5-4e8c-b1e5-a4d7293b1385
id
urn:agi-pathway:uuid-26ce00f6-56f5-4e8c-b1e5-a4d7293b1385
subClassOf
urn:agi-folder:m
urn:agi-folder:mantle_cell_lymphoma
urn:agi-folder:lymphatic_system
type
has_exact_synonym
PathwayType: signaling
PMID: 19880776
CellType: cancer cell
PMID: 18410453
Notes: Headnote: Mantle cell lymphoma (MCL) represents approximately 4-10% of all cases of non-Hodgkin lymphoma. It occurs primarily among elderly individuals with a median age of approximately 60 years (range 29-85). Most MCL patients have disseminated disease including generalized lymphadenopathies and bone marrow involvement. The clinical behavior of MCL patients is aggressive with a median overall survival of approximately 3-4 years. MCL is a mature B-cell neoplasm arising from antigen-experienced B cells. Signaling description:The genetic hallmark of MCL is the translocation t(11;14)(q13;q32) leading to the formation of a fusion gene and protein, IGH-CCND1 and aberrant expression of cyclin D1 (CCND1) which is not typically expressed in normal lymphocytes. At the same time, several observations suggest that CCND1 dysregulation is not sufficient for cell transformation, nor does it explain the aggressive behavior of MCL. Therefore, secondary chromosome alterations are necessary. MCL has the highest degree of genomic instability among B-cell malignances and many secondary chromosomal alterations of cell-cycle regulation genes have been described in MCL. TP53, RB1, ATM, BCL2L11, SOCS1, CDKN2A, CDKN2C, HIC1, FAF1, TNFAIP3, and CHEK2 genes are frequently inactivated by point mutations or gene deletions. In addition, gene amplifications deregulate additional genes including CDK4, BMI1, MDM2, BCL2, MYC, SYK, and PIK3CA while point mutations may activate NOTCH1. Furthermore, several signaling pathways contribute to MCL pathogenesis including constitutively activated PI3K/AKT1/MTOR, NF-kB, WNT, Hedgehog (SHH), Notch, and JAK/STAT pathways. Further, there are some indications that tumor-host interactions may be more important in MCL than currently believed. It has been shown that IL6, IL10, and CXCL12 may activate JAK/STAT3 pathway. The expression of CD40 and responsiveness to CD40LG suggest that MCL cells can interact with CD40LG-positive T cells. Furthermore, epigenetic changes in MCL are currently under investigation. Several hypomethylated and thereby upregulated genes including NOTCH1, CDK5, and HDAC1 could play a pathogenic role in disease development and progression. MCL is one of the most difficult B-cell lymphomas to treat. Although conventional chemotherapy induces high remission rates in previously untreated patients, relapse within a few years is common contributing to a rather short median survival of 3-4 years. Proteasome inhibitors (bortezomib), MTOR inhibitors (temsirolimus), immunomodulatory drugs (lenalidomide) and new alkylating agents (bendamustine) have recently been added to the treatment options for MCL. Outcome effects: In general, all of the described MCL-related signaling routes promote tumor cell proliferation and survival. The role of CCND1 in MCL lymphomagenesis is related to its function as a regulator of cyclin-dependent kinases, CDK4 and CDK6 during the cell cycle. The binding of CCND1 to CDK4/6 activates the transcription factor, E2F by phosphorylating its inhibitor, RB1, and further promoting cyclin E/CDK2 activation to trigger entry into the S phase of the cell cycle. In addition, the microenvironment most likely plays an important role in the biology of MCL. 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.
CellType: B-cell
Organ_System: lymphatic system
Description: Mantle cell lymphoma (MCL) represents approximately 4-10? of all cases of non-Hodgkin lymphoma. MCL is a mature B-cell neoplasm arising from antigen-experienced B cells. Pathway is built manually using published studies.
PMID: 22224767
PMID: 23023712
PMID: 20940415
Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-26ce00f6-56f5-4e8c-b1e5-a4d7293b1385
NodeType: Pathway
Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin
PMID: 19362399
Organ: lymph node
Source: Diseases
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urn:agi-folder:m
urn:agi-folder:mantle_cell_lymphoma
urn:agi-folder:lymphatic_system
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