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postgraduate thesis: JAK-STAT pathway as potential target of acute myeloid leukemia
Title | JAK-STAT pathway as potential target of acute myeloid leukemia |
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Authors | |
Issue Date | 2012 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Han, H. [韓浩俊]. (2012). JAK-STAT pathway as potential target of acute myeloid leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5053420 |
Abstract |
Acute myeloid leukemia (AML) is a group of heterogeneous diseases characterized by an abnormal increase in myeloblasts. Despite intensive chemotherapy and allogeneic bone marrow transplantation, the treatment outcome of AML remains unsatisfactory, with a cure rate of only about 30%. Therefore, novel therapeutic strategies targeting the pathogenetic pathways of leukemia initiation and progression are needed. Using intracellular phospho-flow analysis with normal bone marrow as reference, we detected an increase in phosphorylated-STAT5 (pSTAT5) in three leukemic cell lines (K562, KG-1 and ML-2) and 15 primary AML samples. Treatment with specific JAK2 inhibitor TG101209 and JAK2/3 inhibitor AG490 significantly reduced pSTAT5 level and leukemia cell growth associated with an increase in apoptosis and decrease in cellular proliferation. The clonogenic activities of these leukemia cell lines were also significantly reduced. Furthermore, treatment with these inhibitors in K562 and KG-1 also significantly reduced the WNT signaling activity, as enumerated by the TOP/FLASH luciferase assay. In addition, genes associated with oncogenic potential and anti-apoptosis were significantly reduced, consistent with the pathogenetic role of JAK-STAT pathway.
In summary, the present study highlighted the importance of the JAK2-STAT5 signaling pathway in sustaining AML. The results may open up a new avenue whereby new therapeutic strategies targeting AML can be designed. |
Degree | Master of Philosophy |
Subject | Acute myeloid leukemia Cellular signal transduction. Cytokines. Protein kinases. |
Dept/Program | Medicine |
Persistent Identifier | http://hdl.handle.net/10722/188301 |
HKU Library Item ID | b5053420 |
DC Field | Value | Language |
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dc.contributor.author | Han, Ho-chun. | - |
dc.contributor.author | 韓浩俊. | - |
dc.date.accessioned | 2013-08-27T08:03:27Z | - |
dc.date.available | 2013-08-27T08:03:27Z | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Han, H. [韓浩俊]. (2012). JAK-STAT pathway as potential target of acute myeloid leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5053420 | - |
dc.identifier.uri | http://hdl.handle.net/10722/188301 | - |
dc.description.abstract | Acute myeloid leukemia (AML) is a group of heterogeneous diseases characterized by an abnormal increase in myeloblasts. Despite intensive chemotherapy and allogeneic bone marrow transplantation, the treatment outcome of AML remains unsatisfactory, with a cure rate of only about 30%. Therefore, novel therapeutic strategies targeting the pathogenetic pathways of leukemia initiation and progression are needed. Using intracellular phospho-flow analysis with normal bone marrow as reference, we detected an increase in phosphorylated-STAT5 (pSTAT5) in three leukemic cell lines (K562, KG-1 and ML-2) and 15 primary AML samples. Treatment with specific JAK2 inhibitor TG101209 and JAK2/3 inhibitor AG490 significantly reduced pSTAT5 level and leukemia cell growth associated with an increase in apoptosis and decrease in cellular proliferation. The clonogenic activities of these leukemia cell lines were also significantly reduced. Furthermore, treatment with these inhibitors in K562 and KG-1 also significantly reduced the WNT signaling activity, as enumerated by the TOP/FLASH luciferase assay. In addition, genes associated with oncogenic potential and anti-apoptosis were significantly reduced, consistent with the pathogenetic role of JAK-STAT pathway. In summary, the present study highlighted the importance of the JAK2-STAT5 signaling pathway in sustaining AML. The results may open up a new avenue whereby new therapeutic strategies targeting AML can be designed. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.source.uri | http://hub.hku.hk/bib/B50534208 | - |
dc.subject.lcsh | Acute myeloid leukemia | - |
dc.subject.lcsh | Cellular signal transduction. | - |
dc.subject.lcsh | Cytokines. | - |
dc.subject.lcsh | Protein kinases. | - |
dc.title | JAK-STAT pathway as potential target of acute myeloid leukemia | - |
dc.type | PG_Thesis | - |
dc.identifier.hkul | b5053420 | - |
dc.description.thesisname | Master of Philosophy | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Medicine | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_b5053420 | - |
dc.date.hkucongregation | 2013 | - |
dc.identifier.mmsid | 991035481459703414 | - |