Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function
Epigenetic dysregulation is a hallmark of many haematological malignancies and is very frequent in acute myeloid leukaemia (AML). A cardinal example is the altered activity of the Polycomb Repressive Complex 2 (PRC2) due to somatic mutations and deletions in genes encoding PRC2 core factors that are...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/6/1693 |
| _version_ | 1797612997270568960 |
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| author | Teerna Bhattacharyya Jonathan Bond |
| author_facet | Teerna Bhattacharyya Jonathan Bond |
| author_sort | Teerna Bhattacharyya |
| collection | DOAJ |
| description | Epigenetic dysregulation is a hallmark of many haematological malignancies and is very frequent in acute myeloid leukaemia (AML). A cardinal example is the altered activity of the Polycomb Repressive Complex 2 (PRC2) due to somatic mutations and deletions in genes encoding PRC2 core factors that are necessary for correct complex assembly. These genetic alterations typically lead to reduced histone methyltransferase activity that, in turn, has been strongly linked to poor prognosis and chemoresistance. In this review, we provide an overview of genetic alterations of PRC components in AML, with particular reference to structural and functional features of PRC2 factors. We further review genetic interactions between these alterations and other AML-associated mutations in both adult and paediatric leukaemias. Finally, we discuss reported prognostic links between PRC2 mutations and deletions and disease outcomes and potential implications for therapy. |
| first_indexed | 2024-03-11T06:49:45Z |
| format | Article |
| id | doaj.art-872a72b4c58e41949520c873ea51a1b0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T06:49:45Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-872a72b4c58e41949520c873ea51a1b02023-11-17T10:05:53ZengMDPI AGCancers2072-66942023-03-01156169310.3390/cancers15061693Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to FunctionTeerna Bhattacharyya0Jonathan Bond1Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04V1W8 Dublin 4, IrelandSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04V1W8 Dublin 4, IrelandEpigenetic dysregulation is a hallmark of many haematological malignancies and is very frequent in acute myeloid leukaemia (AML). A cardinal example is the altered activity of the Polycomb Repressive Complex 2 (PRC2) due to somatic mutations and deletions in genes encoding PRC2 core factors that are necessary for correct complex assembly. These genetic alterations typically lead to reduced histone methyltransferase activity that, in turn, has been strongly linked to poor prognosis and chemoresistance. In this review, we provide an overview of genetic alterations of PRC components in AML, with particular reference to structural and functional features of PRC2 factors. We further review genetic interactions between these alterations and other AML-associated mutations in both adult and paediatric leukaemias. Finally, we discuss reported prognostic links between PRC2 mutations and deletions and disease outcomes and potential implications for therapy.https://www.mdpi.com/2072-6694/15/6/1693epigeneticspolycombacute myeloid leukaemiaprotein structuregenetic interactions |
| spellingShingle | Teerna Bhattacharyya Jonathan Bond Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function Cancers epigenetics polycomb acute myeloid leukaemia protein structure genetic interactions |
| title | Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function |
| title_full | Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function |
| title_fullStr | Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function |
| title_full_unstemmed | Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function |
| title_short | Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function |
| title_sort | polycomb alterations in acute myeloid leukaemia from structure to function |
| topic | epigenetics polycomb acute myeloid leukaemia protein structure genetic interactions |
| url | https://www.mdpi.com/2072-6694/15/6/1693 |
| work_keys_str_mv | AT teernabhattacharyya polycombalterationsinacutemyeloidleukaemiafromstructuretofunction AT jonathanbond polycombalterationsinacutemyeloidleukaemiafromstructuretofunction |