Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis
Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloprolif...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Platelets |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/09537104.2024.2304173 |
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| _version_ | 1850148674744614912 |
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| author | Ryan J Collinson Lynne Wilson Darren Boey Zi Yun Ng Bob Mirzai Hun S Chuah Rebecca Howman Carolyn S Grove Jacques A J Malherbe Michael F Leahy Matthew D Linden Kathryn A Fuller Wendy N Erber Belinda B Guo |
| author_facet | Ryan J Collinson Lynne Wilson Darren Boey Zi Yun Ng Bob Mirzai Hun S Chuah Rebecca Howman Carolyn S Grove Jacques A J Malherbe Michael F Leahy Matthew D Linden Kathryn A Fuller Wendy N Erber Belinda B Guo |
| author_sort | Ryan J Collinson |
| collection | DOAJ |
| description | Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise de novo or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical “MF-like” morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of TCF3 in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets. |
| format | Article |
| id | doaj-art-8a8bf5c785ff42dba6fe62c17e84f290 |
| institution | OA Journals |
| issn | 0953-7104 1369-1635 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj-art-8a8bf5c785ff42dba6fe62c17e84f2902025-08-20T02:27:11ZengTaylor & Francis GroupPlatelets0953-71041369-16352024-12-0135110.1080/09537104.2024.2304173Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosisRyan J Collinson0Lynne Wilson1Darren Boey2Zi Yun Ng3Bob Mirzai4Hun S Chuah5Rebecca Howman6Carolyn S Grove7Jacques A J Malherbe8Michael F Leahy9Matthew D Linden10Kathryn A Fuller11Wendy N Erber12Belinda B Guo13School of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaPathWest Laboratory Medicine, Nedlands, WA, AustraliaDepartment of Haematology, Royal Perth Hospital, Perth, WA, AustraliaDepartment of Haematology, Sir Charles Gairdner Hospital Nedlands AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaDepartment of Haematology, Fiona Stanley Hospital, Murdoch, WA, AustraliaDepartment of Haematology, Royal Perth Hospital, Perth, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Crawley, WA, AustraliaTranscription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise de novo or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical “MF-like” morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of TCF3 in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.https://www.tandfonline.com/doi/10.1080/09537104.2024.2304173Megakaryocytemyelofibrosismyeloproliferative neoplasmsnext-generation sequencingplateletsTCF3 |
| spellingShingle | Ryan J Collinson Lynne Wilson Darren Boey Zi Yun Ng Bob Mirzai Hun S Chuah Rebecca Howman Carolyn S Grove Jacques A J Malherbe Michael F Leahy Matthew D Linden Kathryn A Fuller Wendy N Erber Belinda B Guo Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis Platelets Megakaryocyte myelofibrosis myeloproliferative neoplasms next-generation sequencing platelets TCF3 |
| title | Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis |
| title_full | Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis |
| title_fullStr | Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis |
| title_full_unstemmed | Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis |
| title_short | Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis |
| title_sort | transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis |
| topic | Megakaryocyte myelofibrosis myeloproliferative neoplasms next-generation sequencing platelets TCF3 |
| url | https://www.tandfonline.com/doi/10.1080/09537104.2024.2304173 |
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