The mutational landscape of myeloid leukaemia in down syndrome
de Castro, Carini Picardi Morais (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Cadefau-Fabregat, Maria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cuartero, Sergi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	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.
Grants:	"la Caixa" Foundation JLF#1902
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Myeloid leukaemia ; Down syndrome ; Trisomy 21 ; Acute megakaryoblastic leukaemia (AMKL) ; Transcription ; Chromatin ; Signalling
Published in:	Cancers, Vol. 13 Núm. 16 (august 2021) , p. 4144, ISSN 2072-6694

DOI: 10.3390/cancers13164144
PMID: 34439298

18 p, 1.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles