The mechanism of action of the negative Regulators of jak/stat singnaling pathway in Resistant FLT-ITD acute myeloid leukaemia cells
The aim of this study was to understand the mechanism of action of negative regulators of JAK/STAT signalling pathway in FLT3-ITD AML cell lines with different response towards the FLT3 inhibitors PKC412 and CEP701. The cytotoxic dose of CEP-701 and PKC-412 on resistant cell lines was significant...
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| Format: | Article |
| Language: | English |
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Pusat Pengajian Sains Perubatan, Universiti Sains Malaysia
2019
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| Online Access: | http://eprints.usm.my/51676/1/DR.%20MUHAMMAD%20FARID%20JOHAN-Eprints.pdf |
| _version_ | 1825906535134396416 |
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| author | Johan, Muhammad Farid |
| author_facet | Johan, Muhammad Farid |
| author_sort | Johan, Muhammad Farid |
| collection | USM |
| description | The aim of this study was to understand the mechanism of action of negative regulators of
JAK/STAT signalling pathway in FLT3-ITD AML cell lines with different response towards the
FLT3 inhibitors PKC412 and CEP701. The cytotoxic dose of CEP-701 and PKC-412 on resistant
cell lines was significantly higher in comparison with parental and MV4-11 R-cep+5-Aza (p=0.004)
and MV4-11pkc+5-Aza (p=0.003). The resistant cells showed a significant higher viability and
lower apoptosis compared with others (p<0.001 ). Expression of SHP-1 and PRG2 were 7 and 20-
folds higher in MV4-11R-cep+5-Aza compared to parental and resistant (p=0.011). There was
significant hypomethylation (p=0.002) in CpG islands of SHP-1 and PRG2, associated with their
re-expressions. The higher sensitivity to TKI was associated with STAT3 inactivation in 5-Aza
treated compared with their resistant cell lines. 20-PAGE showed the number of protein spots
detected were 522±29 with 79% matching rate which resulted in three upregulated proteins. The
restoration of SHP-1 and PRG2 expression induces sensitivity towards CEP-701. 5-Aza
enhances efficacy of TKI and treatment with 5-Aza followed by PKC-412 or CEP-701 could
provide suitable candidates for further investigates to underline alternative options for the
treatment of AML patients with FL T3-ITD. |
| first_indexed | 2024-03-06T15:51:03Z |
| format | Article |
| id | usm.eprints-51676 |
| institution | Universiti Sains Malaysia |
| language | English |
| last_indexed | 2024-03-06T15:51:03Z |
| publishDate | 2019 |
| publisher | Pusat Pengajian Sains Perubatan, Universiti Sains Malaysia |
| record_format | dspace |
| spelling | usm.eprints-516762022-02-27T03:44:46Z http://eprints.usm.my/51676/ The mechanism of action of the negative Regulators of jak/stat singnaling pathway in Resistant FLT-ITD acute myeloid leukaemia cells Johan, Muhammad Farid R Medicine The aim of this study was to understand the mechanism of action of negative regulators of JAK/STAT signalling pathway in FLT3-ITD AML cell lines with different response towards the FLT3 inhibitors PKC412 and CEP701. The cytotoxic dose of CEP-701 and PKC-412 on resistant cell lines was significantly higher in comparison with parental and MV4-11 R-cep+5-Aza (p=0.004) and MV4-11pkc+5-Aza (p=0.003). The resistant cells showed a significant higher viability and lower apoptosis compared with others (p<0.001 ). Expression of SHP-1 and PRG2 were 7 and 20- folds higher in MV4-11R-cep+5-Aza compared to parental and resistant (p=0.011). There was significant hypomethylation (p=0.002) in CpG islands of SHP-1 and PRG2, associated with their re-expressions. The higher sensitivity to TKI was associated with STAT3 inactivation in 5-Aza treated compared with their resistant cell lines. 20-PAGE showed the number of protein spots detected were 522±29 with 79% matching rate which resulted in three upregulated proteins. The restoration of SHP-1 and PRG2 expression induces sensitivity towards CEP-701. 5-Aza enhances efficacy of TKI and treatment with 5-Aza followed by PKC-412 or CEP-701 could provide suitable candidates for further investigates to underline alternative options for the treatment of AML patients with FL T3-ITD. Pusat Pengajian Sains Perubatan, Universiti Sains Malaysia 2019 Article NonPeerReviewed application/pdf en http://eprints.usm.my/51676/1/DR.%20MUHAMMAD%20FARID%20JOHAN-Eprints.pdf Johan, Muhammad Farid (2019) The mechanism of action of the negative Regulators of jak/stat singnaling pathway in Resistant FLT-ITD acute myeloid leukaemia cells. The mechanism of action of the negative Regulators of jak/stat singnaling pathway in Resistant FLT-ITD acute myeloid leukaemia cells. |
| spellingShingle | R Medicine Johan, Muhammad Farid The mechanism of action of the negative Regulators of jak/stat singnaling pathway in Resistant FLT-ITD acute myeloid leukaemia cells |
| title | The mechanism of action of the negative
Regulators of jak/stat singnaling pathway in
Resistant FLT-ITD acute myeloid leukaemia cells |
| title_full | The mechanism of action of the negative
Regulators of jak/stat singnaling pathway in
Resistant FLT-ITD acute myeloid leukaemia cells |
| title_fullStr | The mechanism of action of the negative
Regulators of jak/stat singnaling pathway in
Resistant FLT-ITD acute myeloid leukaemia cells |
| title_full_unstemmed | The mechanism of action of the negative
Regulators of jak/stat singnaling pathway in
Resistant FLT-ITD acute myeloid leukaemia cells |
| title_short | The mechanism of action of the negative
Regulators of jak/stat singnaling pathway in
Resistant FLT-ITD acute myeloid leukaemia cells |
| title_sort | mechanism of action of the negative regulators of jak stat singnaling pathway in resistant flt itd acute myeloid leukaemia cells |
| topic | R Medicine |
| url | http://eprints.usm.my/51676/1/DR.%20MUHAMMAD%20FARID%20JOHAN-Eprints.pdf |
| work_keys_str_mv | AT johanmuhammadfarid themechanismofactionofthenegativeregulatorsofjakstatsingnalingpathwayinresistantfltitdacutemyeloidleukaemiacells AT johanmuhammadfarid mechanismofactionofthenegativeregulatorsofjakstatsingnalingpathwayinresistantfltitdacutemyeloidleukaemiacells |