loading...| Preferred Name |
B-Cell Chronic Lymphocytic Leukemia |
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| Synonyms |
PathwayType: signaling Tissue: blood CellType: cancer cell CellType: B-cell Organ_System: lymphatic system PMID: 21239773 Description: B-cell chronic lymphocytic leukemia (B-CLL) is a malignant lymphoproliferative disorder of mature non-functional B lymphocytes. B-CLL is the most common form of leukemia in Western countries. Pathway is built manually using published studies. Tissue: bone marrow PMID: 18035318 PMID: 20863894 PMID: 22160019 Notes: Headnote: B-cell chronic lymphocytic leukemia (B-CLL) is a malignant lymphoproliferative disorder of mature non-functional B-lymphocytes. B-CLL is the most common form of leukemia in Western countries. It is a disease of adults, with most patients being over 50. Approximately 5-10% of patients report a family history of leukemia or lymphoma. The progressive accumulation of monoclonal B-lymphocytes leads to leukocytosis, lymphadenopathy, hepatosplenomegaly, bone marrow failure, recurrent infection and is sometimes associated with autoimmune disease (hemolytic anemia and autoimmune thrombocytopenia). Signaling description: There are two subsets of B-CLL cases that can be differentiated by the degree of somatic hypermutation (mutated and unmutated immunoglobulin heavy chain variable region (IGHV) genes) and have distinct clinical and biological behaviors. IGHV-mutated B-CLL group has low CD38 and ZAP70 expression, long telomeres, is less responsive to BCR stimulation, and is genetically stable with a favorable prognosis.IGHV-unmutated B-CLL has the opposite properties: it has high CD38 and ZAP70 expression, short telomeres, is responsive to BCR stimulation, and is genetically unstable with an unfavorable prognosis. Approximately 80% of CLLs show aberrations in a few frequently affected chromosomal regions, including 13q14 (MIR15A and MIR16-1), 11q23 (ataxia telangiectasia-mutated; ATM), trisomy 12 and 17p13 (TP53). Recurrent translocations are rare in CLL. The p53 tumor suppressor (TP53) gene is a transcription factor that is involved in cell cycle arrest and the induction of apoptosis in genetically damaged cells. B-CLL patients with a p53 deletion exhibit a very poor overall survival and often fail to respond to treatment. Therefore, p53 plays a central role in understanding the lack of response to therapy. Single nucleotide polymorphisms (SNPs) in the interferon regulatory factor 4 (IRF4) gene were shown to be associated with a predisposition to the familial form of B-CLL. IRF4 is a known regulator of lymphocyte development and proliferation. In addition, molecular interactions between CLL and microenvironment are considered important for B-CLL cell survival and proliferation. The contact between B-CLL cells and monocyte-derived nurse-like cells or stromal cells is established and maintained by chemokine receptors and adhesion molecules. B-CLL is a disease caused by a loss of appropriate apoptosis, rather than increased proliferation. The great majority (98%) of peripherally circulating B-CLL cells is arrested in G0 or the early G1 phase and has overexpression of antiapoptotic proteins. Circulating B-CLL cells can survive for a few months (as opposed to a few days for normal B-cells). CDKN1B has been shown to play a critical role in cell cycle arrest of B-CLL cells. There is only a small proliferative compartment of B-CLL cells in bone marrow. Outcome effects: TNFR, BCR, TLR signaling, as well as NF-kB, PI3K/Akt, RAS/MAPK and MTOR pathways are all involved in the pathogenesis of B-CLL. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. NodeType: Pathway PMID: 17707830 Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 22973499 PMID: 18059180 PMID: 19956173 Source: Diseases Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-d5d8e0b2-8ebf-4879-aced-e6755f334525 |
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| ID |
urn:agi-pathway:uuid-d5d8e0b2-8ebf-4879-aced-e6755f334525 |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Source |
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| has_exact_synonym |
PathwayType: signaling Tissue: blood CellType: cancer cell CellType: B-cell Organ_System: lymphatic system PMID: 21239773 Description: B-cell chronic lymphocytic leukemia (B-CLL) is a malignant lymphoproliferative disorder of mature non-functional B lymphocytes. B-CLL is the most common form of leukemia in Western countries. Pathway is built manually using published studies. Tissue: bone marrow PMID: 18035318 PMID: 20863894 PMID: 22160019 Notes: Headnote: B-cell chronic lymphocytic leukemia (B-CLL) is a malignant lymphoproliferative disorder of mature non-functional B-lymphocytes. B-CLL is the most common form of leukemia in Western countries. It is a disease of adults, with most patients being over 50. Approximately 5-10% of patients report a family history of leukemia or lymphoma. The progressive accumulation of monoclonal B-lymphocytes leads to leukocytosis, lymphadenopathy, hepatosplenomegaly, bone marrow failure, recurrent infection and is sometimes associated with autoimmune disease (hemolytic anemia and autoimmune thrombocytopenia). Signaling description: There are two subsets of B-CLL cases that can be differentiated by the degree of somatic hypermutation (mutated and unmutated immunoglobulin heavy chain variable region (IGHV) genes) and have distinct clinical and biological behaviors. IGHV-mutated B-CLL group has low CD38 and ZAP70 expression, long telomeres, is less responsive to BCR stimulation, and is genetically stable with a favorable prognosis.IGHV-unmutated B-CLL has the opposite properties: it has high CD38 and ZAP70 expression, short telomeres, is responsive to BCR stimulation, and is genetically unstable with an unfavorable prognosis. Approximately 80% of CLLs show aberrations in a few frequently affected chromosomal regions, including 13q14 (MIR15A and MIR16-1), 11q23 (ataxia telangiectasia-mutated; ATM), trisomy 12 and 17p13 (TP53). Recurrent translocations are rare in CLL. The p53 tumor suppressor (TP53) gene is a transcription factor that is involved in cell cycle arrest and the induction of apoptosis in genetically damaged cells. B-CLL patients with a p53 deletion exhibit a very poor overall survival and often fail to respond to treatment. Therefore, p53 plays a central role in understanding the lack of response to therapy. Single nucleotide polymorphisms (SNPs) in the interferon regulatory factor 4 (IRF4) gene were shown to be associated with a predisposition to the familial form of B-CLL. IRF4 is a known regulator of lymphocyte development and proliferation. In addition, molecular interactions between CLL and microenvironment are considered important for B-CLL cell survival and proliferation. The contact between B-CLL cells and monocyte-derived nurse-like cells or stromal cells is established and maintained by chemokine receptors and adhesion molecules. B-CLL is a disease caused by a loss of appropriate apoptosis, rather than increased proliferation. The great majority (98%) of peripherally circulating B-CLL cells is arrested in G0 or the early G1 phase and has overexpression of antiapoptotic proteins. Circulating B-CLL cells can survive for a few months (as opposed to a few days for normal B-cells). CDKN1B has been shown to play a critical role in cell cycle arrest of B-CLL cells. There is only a small proliferative compartment of B-CLL cells in bone marrow. Outcome effects: TNFR, BCR, TLR signaling, as well as NF-kB, PI3K/Akt, RAS/MAPK and MTOR pathways are all involved in the pathogenesis of B-CLL. Highlighted proteins: Proteins with increased expression or activity are highlighted in red, and proteins with decreased expression or activity are highlighted in blue. NodeType: Pathway PMID: 17707830 Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin PMID: 22973499 PMID: 18059180 PMID: 19956173 Source: Diseases |
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| id |
urn:agi-pathway:uuid-d5d8e0b2-8ebf-4879-aced-e6755f334525 |
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| label |
B-Cell Chronic Lymphocytic Leukemia |
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| notation |
uuid-d5d8e0b2-8ebf-4879-aced-e6755f334525 |
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| prefLabel |
B-Cell Chronic Lymphocytic Leukemia |
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| treeView |
urn:agi-folder:b urn:agi-folder:blood urn:agi-folder:lymphatic_system urn:agi-folder:b-cell_chronic_lymphocytic_leukemia |
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| subClassOf |
urn:agi-folder:b urn:agi-folder:blood urn:agi-folder:lymphatic_system urn:agi-folder:b-cell_chronic_lymphocytic_leukemia |