The mutational landscape of myeloid leukaemia in down syndrome

Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives...

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Autores: de Castro, Carini Picardi Morais, Cadefau-Fabregat, Maria|||0000-0001-5915-3202, Cuartero, Sergi|||0000-0002-9338-583X
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:270574
Acceso en línea:https://ddd.uab.cat/record/270574
https://dx.doi.org/urn:doi:10.3390/cancers13164144
Access Level:acceso abierto
Palabra clave:Myeloid leukaemia
Down syndrome
Trisomy 21
Acute megakaryoblastic leukaemia (AMKL)
Transcription
Chromatin
Signalling
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spelling The mutational landscape of myeloid leukaemia in down syndromede Castro, Carini Picardi MoraisCadefau-Fabregat, Maria|||0000-0001-5915-3202Cuartero, Sergi|||0000-0002-9338-583XMyeloid leukaemiaDown syndromeTrisomy 21Acute megakaryoblastic leukaemia (AMKL)TranscriptionChromatinSignallingChildren with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS). These secondary mutations are predominantly found in chromatin and epigenetic regulators-such as cohesin, CTCF or EZH2-and in signalling mediators of the JAK/STAT and RAS pathways. Most of them are also found in non-DS myeloid malignancies, albeit at extremely different frequencies. Intriguingly, mutations in proteins involved in the three-dimensional organization of the genome are found in nearly 50% of cases. How the resulting mutant proteins cooperate with trisomy 21 and mutant GATA1 to promote ML-DS is not fully understood. In this review, we summarize and discuss current knowledge about the sequential acquisition of genomic alterations in ML-DS.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/270574https://dx.doi.org/urn:doi:10.3390/cancers13164144reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaIngléseng"la Caixa" Foundation https://doi.org/10.13039/100010434 JLF#1902open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2705742026-06-06T12:50:31Z
dc.title.none.fl_str_mv The mutational landscape of myeloid leukaemia in down syndrome
title The mutational landscape of myeloid leukaemia in down syndrome
spellingShingle The mutational landscape of myeloid leukaemia in down syndrome
de Castro, Carini Picardi Morais
Myeloid leukaemia
Down syndrome
Trisomy 21
Acute megakaryoblastic leukaemia (AMKL)
Transcription
Chromatin
Signalling
title_short The mutational landscape of myeloid leukaemia in down syndrome
title_full The mutational landscape of myeloid leukaemia in down syndrome
title_fullStr The mutational landscape of myeloid leukaemia in down syndrome
title_full_unstemmed The mutational landscape of myeloid leukaemia in down syndrome
title_sort The mutational landscape of myeloid leukaemia in down syndrome
dc.creator.none.fl_str_mv de Castro, Carini Picardi Morais
Cadefau-Fabregat, Maria|||0000-0001-5915-3202
Cuartero, Sergi|||0000-0002-9338-583X
author de Castro, Carini Picardi Morais
author_facet de Castro, Carini Picardi Morais
Cadefau-Fabregat, Maria|||0000-0001-5915-3202
Cuartero, Sergi|||0000-0002-9338-583X
author_role author
author2 Cadefau-Fabregat, Maria|||0000-0001-5915-3202
Cuartero, Sergi|||0000-0002-9338-583X
author2_role author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Myeloid leukaemia
Down syndrome
Trisomy 21
Acute megakaryoblastic leukaemia (AMKL)
Transcription
Chromatin
Signalling
topic Myeloid leukaemia
Down syndrome
Trisomy 21
Acute megakaryoblastic leukaemia (AMKL)
Transcription
Chromatin
Signalling
description Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS). These secondary mutations are predominantly found in chromatin and epigenetic regulators-such as cohesin, CTCF or EZH2-and in signalling mediators of the JAK/STAT and RAS pathways. Most of them are also found in non-DS myeloid malignancies, albeit at extremely different frequencies. Intriguingly, mutations in proteins involved in the three-dimensional organization of the genome are found in nearly 50% of cases. How the resulting mutant proteins cooperate with trisomy 21 and mutant GATA1 to promote ML-DS is not fully understood. In this review, we summarize and discuss current knowledge about the sequential acquisition of genomic alterations in ML-DS.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/270574
https://dx.doi.org/urn:doi:10.3390/cancers13164144
url https://ddd.uab.cat/record/270574
https://dx.doi.org/urn:doi:10.3390/cancers13164144
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv "la Caixa" Foundation https://doi.org/10.13039/100010434 JLF#1902
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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