Advances in germline predisposition to acute leukaemias and myeloid neoplasms

Although much work has focused on the elucidation of somatic alterations that drive the development of acute leukaemias and other haematopoietic diseases, it has become increasingly recognized that germline mutations are common in many of these neoplasms. In this Review, we highlight the different g...

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Veröffentlicht in:	Nature reviews. Cancer Jg. 21; H. 2; S. 122 - 137
Hauptverfasser:	Klco, Jeffery M., Mullighan, Charles G.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 01.02.2021 Nature Publishing Group
Schlagworte:	631/208/68 631/67/1990/283 631/67/2332 631/67/69 692/499 Acute lymphoblastic leukemia Acute myeloid leukemia Biomedical and Life Sciences Biomedicine Blood cancer Cancer Cancer Research Children Development and progression Disease Progression Gene mutations Genetic aspects Genetic Predisposition to Disease - genetics Germ-Line Mutation - genetics Health aspects Hematology Humans Leukemia Leukemia, Myeloid, Acute - genetics Mutation Myelodysplastic syndrome Myelodysplastic syndromes Myelodysplastic Syndromes - genetics Oncology, Experimental p53 Protein Phenotype Phenotypes Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Review Article Risk factors Runx1 protein Somatic cells Tumors Uranium United States
ISSN:	1474-175X, 1474-1768, 1474-1768
Online-Zugang:	Volltext
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Zusammenfassung:	Although much work has focused on the elucidation of somatic alterations that drive the development of acute leukaemias and other haematopoietic diseases, it has become increasingly recognized that germline mutations are common in many of these neoplasms. In this Review, we highlight the different genetic pathways impacted by germline mutations that can ultimately lead to the development of familial and sporadic haematological malignancies, including acute lymphoblastic leukaemia, acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Many of the genes disrupted by somatic mutations in these diseases (for example, TP53 , RUNX1 , IKZF1 and ETV6 ) are the same as those that harbour germline mutations in children and adolescents who develop these malignancies. Moreover, the presumption that familial leukaemias only present in childhood is no longer true, in large part due to the numerous studies demonstrating germline DDX41 mutations in adults with MDS and AML. Lastly, we highlight how different cooperating events can influence the ultimate phenotype in these different familial leukaemia syndromes. This Review highlights the different genetic pathways impacted by germline mutations that can lead to the development of familial and sporadic haematological malignancies, with a particular focus on recent advances in acute lymphoblastic leukaemia, acute myeloid leukaemia and myelodysplastic syndromes.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	1474-175X 1474-1768 1474-1768
DOI:	10.1038/s41568-020-00315-z