Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation
Wuhan Hui, Wei Zhang, Congyan Liu, Suigui Wan, Wanling Sun, Li Su Department of Hematology, Xuan Wu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Li SuDepartment of Hematology, Xuan Wu Hospital, Capital Medical University, Beijing, People’s Republic of Chin...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-08-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/alterations-of-signaling-pathways-in-essential-thrombocythemia-with-ca-peer-reviewed-fulltext-article-CMAR |
| _version_ | 1818832916849885184 |
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| author | Hui W Zhang W Liu C Wan S Sun W Su L |
| author_facet | Hui W Zhang W Liu C Wan S Sun W Su L |
| author_sort | Hui W |
| collection | DOAJ |
| description | Wuhan Hui, Wei Zhang, Congyan Liu, Suigui Wan, Wanling Sun, Li Su Department of Hematology, Xuan Wu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Li SuDepartment of Hematology, Xuan Wu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel/Fax +86-10-83198476Email suli@xwhosp.orgPurpose: Though mutations of the calreticulin (CALR) gene have been identified in essential thrombocythemia patients, the detailed mechanisms for CALR mutations have not been completely clarified. Our study is aimed at characterizing alteration of protein expression in ET patients with mutated CALRdel52 and further recognizing possible involvement of signaling pathways associated with CALR mutations.Patients and Methods: Protein pathway array was performed to analyze the expression levels of proteins involved in various signaling pathways in peripheral blood neutrophils from 18 ET patients with mutated CALRdel52, 20 ET patients with JAK2V617F mutation and 20 controls.Results: We found 20 proteins differentially expressed in ET patients with mutated CALRdel52 compared with healthy controls. These proteins were associated with molecular mechanisms of cancer in ingenuity pathways analysis (IPA) network. We identified top ten canonical pathways which including apoptotic pathways and cellular cytokine pathways might participate in pathogenesis of ET with mutated CALRdel52. Additionally, there were 8 proteins found to be dysregulated differently between ET patients with mutated CALRdel52 and those with JAK2V617F mutation. These proteins might be related to the unique signaling pathways activated by CALRdel52 mutation which were different to JAK/STATs pathway by JAK2V617F mutation.Conclusion: Our study demonstrated that numerous alterations of signaling proteins and pathways in ET patients with mutated CALRdel52. These findings could help to gain insights into the pathological mechanisms of ET.Keywords: essential thrombocytosis, CALRdel52 mutation, protein pathway array, signaling proteins |
| first_indexed | 2024-12-19T02:10:38Z |
| format | Article |
| id | doaj.art-b44f3f32eadc473ab16349bc76798f68 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-19T02:10:38Z |
| publishDate | 2021-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-b44f3f32eadc473ab16349bc76798f682022-12-21T20:40:48ZengDove Medical PressCancer Management and Research1179-13222021-08-01Volume 136231623867625Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin MutationHui WZhang WLiu CWan SSun WSu LWuhan Hui, Wei Zhang, Congyan Liu, Suigui Wan, Wanling Sun, Li Su Department of Hematology, Xuan Wu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Li SuDepartment of Hematology, Xuan Wu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel/Fax +86-10-83198476Email suli@xwhosp.orgPurpose: Though mutations of the calreticulin (CALR) gene have been identified in essential thrombocythemia patients, the detailed mechanisms for CALR mutations have not been completely clarified. Our study is aimed at characterizing alteration of protein expression in ET patients with mutated CALRdel52 and further recognizing possible involvement of signaling pathways associated with CALR mutations.Patients and Methods: Protein pathway array was performed to analyze the expression levels of proteins involved in various signaling pathways in peripheral blood neutrophils from 18 ET patients with mutated CALRdel52, 20 ET patients with JAK2V617F mutation and 20 controls.Results: We found 20 proteins differentially expressed in ET patients with mutated CALRdel52 compared with healthy controls. These proteins were associated with molecular mechanisms of cancer in ingenuity pathways analysis (IPA) network. We identified top ten canonical pathways which including apoptotic pathways and cellular cytokine pathways might participate in pathogenesis of ET with mutated CALRdel52. Additionally, there were 8 proteins found to be dysregulated differently between ET patients with mutated CALRdel52 and those with JAK2V617F mutation. These proteins might be related to the unique signaling pathways activated by CALRdel52 mutation which were different to JAK/STATs pathway by JAK2V617F mutation.Conclusion: Our study demonstrated that numerous alterations of signaling proteins and pathways in ET patients with mutated CALRdel52. These findings could help to gain insights into the pathological mechanisms of ET.Keywords: essential thrombocytosis, CALRdel52 mutation, protein pathway array, signaling proteinshttps://www.dovepress.com/alterations-of-signaling-pathways-in-essential-thrombocythemia-with-ca-peer-reviewed-fulltext-article-CMARessential thrombocytosiscalrdel52 mutationprotein pathway arraysignaling proteins |
| spellingShingle | Hui W Zhang W Liu C Wan S Sun W Su L Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation Cancer Management and Research essential thrombocytosis calrdel52 mutation protein pathway array signaling proteins |
| title | Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation |
| title_full | Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation |
| title_fullStr | Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation |
| title_full_unstemmed | Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation |
| title_short | Alterations of Signaling Pathways in Essential Thrombocythemia with Calreticulin Mutation |
| title_sort | alterations of signaling pathways in essential thrombocythemia with calreticulin mutation |
| topic | essential thrombocytosis calrdel52 mutation protein pathway array signaling proteins |
| url | https://www.dovepress.com/alterations-of-signaling-pathways-in-essential-thrombocythemia-with-ca-peer-reviewed-fulltext-article-CMAR |
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