Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
15
05
2019
accepted:
17
11
2019
revised:
28
10
2019
pubmed:
30
11
2019
medline:
8
10
2020
entrez:
29
11
2019
Statut:
ppublish
Résumé
Juvenile myelomonocytic leukemia (JMML) is a rare aggressive myelodysplastic/myeloproliferative neoplasm of early childhood, initiated by RAS-activating mutations. Genomic analyses have recently described JMML mutational landscape; however, the nature of JMML-propagating cells (JMML-PCs) and the clonal architecture of the disease remained until now elusive. Combining genomic (exome, RNA-seq), Colony forming assay and xenograft studies, we detect the presence of JMML-PCs that faithfully reproduce JMML features including the complex/nonlinear organization of dominant/minor clones, both at diagnosis and relapse. Further integrated analysis also reveals that although the mutations are acquired in hematopoietic stem cells, JMML-PCs are not always restricted to this compartment, highlighting the heterogeneity of the disease during the initiation steps. We show that the hematopoietic stem/progenitor cell phenotype is globally maintained in JMML despite overexpression of CD90/THY-1 in a subset of patients. This study shed new lights into the ontogeny of JMML, and the identity of JMML-PCs, and provides robust models to monitor the disease and test novel therapeutic approaches.
Identifiants
pubmed: 31776464
doi: 10.1038/s41375-019-0662-y
pii: 10.1038/s41375-019-0662-y
pmc: PMC7266742
mid: EMS84957
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1658-1668Subventions
Organisme : Arthritis Research UK
ID : FC001045
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001045
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001045
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001045
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
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