loading...| Preferred Name | Chronic Myeloid Leukemia | |
| Synonyms |
PathwayType: signaling Tissue: blood CellType: cancer cell PMID: 20592475 PMID: 22632137 PMID: 18827185 CellType: leukocyte Organ_System: hematological system Description: Chronic myeloid leukemia is a hematological cancer characterized by the increased and deregulated proliferation of myeloid cells. BCR/ABL is believed to be the primary cause of the chronic phase of CML. Pathway is built manually using published studies. Tissue: bone marrow PMID: 16484590 PMID: 21098337 PMID: 21302608 PMID: 18024655 PMID: 17288299 NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin CellType: myeloblast Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-ab743729-c9ec-43bb-bd97-342b684942df Notes: Headnote: Chronic myeloid or myelogenous leukemia (CML) is a clonal bone marrow stem cell disorder characterized by the increased and unregulated proliferation of predominantly myeloid cells. The main finding in this disease is an elevated level of mature granulocytes and their precursors in bone marrow and blood. Signaling description: CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation, that forms the Philadelphia (Ph) chromosome. The resulting BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which has constitutive tyrosine kinase activity. BCR/ABL activates PI3K/Akt/MTOR, NF-kB, and RAS/MAPK pathways. BCR/ABL also directly activates STAT5A and MYC. In CML cells, the BCR/ABL fusion protein can increase the activity of SMAD3 and 4 promoters and enhance TGFB signaling. The main target in CML is BCR/ABL which can be inactivated by target therapy such as Imatinib, Dasatinib, and Nilotinib (AMN-107). While BCR/ABL is believed to be the primary cause of the chronic phase of CML, the progression to blast crisis requires other molecular changes such as mutations in GATA2, CDKN2A, RUNX1, and TP53. Additional chromosome translocations may be found which generate AML1-EVI1 and AML1-ETO fusion proteins. Consistent with the early stem cell nature of CML, blastic transformation may be myeloid, lymphoid, or undifferentiated/mixed, with myeloid blast crisis being about two times more common than lymphoid. These secondary genetic abnormalities are regarded as probable reasons for drug resistance and are potential therapeutic targets. Outcome effects: As a result, oncogenic signaling leads to block of apoptosis, increased proliferation, and oncogenic protein translation as well as the disruption of DNA repair. TGFB signaling leads to the inhibition of hematopoietic progenitor 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. PMID: 15271392 Source: Diseases |
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urn:agi-pathway:uuid-ab743729-c9ec-43bb-bd97-342b684942df |
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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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PathwayType: signaling Tissue: blood CellType: cancer cell PMID: 20592475 PMID: 22632137 PMID: 18827185 CellType: leukocyte Organ_System: hematological system Description: Chronic myeloid leukemia is a hematological cancer characterized by the increased and deregulated proliferation of myeloid cells. BCR/ABL is believed to be the primary cause of the chronic phase of CML. Pathway is built manually using published studies. Tissue: bone marrow PMID: 16484590 PMID: 21098337 PMID: 21302608 PMID: 18024655 PMID: 17288299 NodeType: Pathway Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin CellType: myeloblast Notes: Headnote: Chronic myeloid or myelogenous leukemia (CML) is a clonal bone marrow stem cell disorder characterized by the increased and unregulated proliferation of predominantly myeloid cells. The main finding in this disease is an elevated level of mature granulocytes and their precursors in bone marrow and blood. Signaling description: CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation, that forms the Philadelphia (Ph) chromosome. The resulting BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which has constitutive tyrosine kinase activity. BCR/ABL activates PI3K/Akt/MTOR, NF-kB, and RAS/MAPK pathways. BCR/ABL also directly activates STAT5A and MYC. In CML cells, the BCR/ABL fusion protein can increase the activity of SMAD3 and 4 promoters and enhance TGFB signaling. The main target in CML is BCR/ABL which can be inactivated by target therapy such as Imatinib, Dasatinib, and Nilotinib (AMN-107). While BCR/ABL is believed to be the primary cause of the chronic phase of CML, the progression to blast crisis requires other molecular changes such as mutations in GATA2, CDKN2A, RUNX1, and TP53. Additional chromosome translocations may be found which generate AML1-EVI1 and AML1-ETO fusion proteins. Consistent with the early stem cell nature of CML, blastic transformation may be myeloid, lymphoid, or undifferentiated/mixed, with myeloid blast crisis being about two times more common than lymphoid. These secondary genetic abnormalities are regarded as probable reasons for drug resistance and are potential therapeutic targets. Outcome effects: As a result, oncogenic signaling leads to block of apoptosis, increased proliferation, and oncogenic protein translation as well as the disruption of DNA repair. TGFB signaling leads to the inhibition of hematopoietic progenitor 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. PMID: 15271392 Source: Diseases |
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| id |
urn:agi-pathway:uuid-ab743729-c9ec-43bb-bd97-342b684942df |
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| label |
Chronic Myeloid Leukemia |
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| notation |
uuid-ab743729-c9ec-43bb-bd97-342b684942df |
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| prefLabel |
Chronic Myeloid Leukemia |
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| treeView |
urn:agi-folder:c urn:agi-folder:chronic_myeloid_leukemia urn:agi-folder:hematological_system urn:agi-folder:blood |
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| subClassOf |
urn:agi-folder:c urn:agi-folder:chronic_myeloid_leukemia urn:agi-folder:hematological_system urn:agi-folder:blood |