Caye, Aurélie, Rouault-Pierre, Kevin, Strullu, Marion, Lainey, Elodie, Abarrategi, Ander, Fenneteau, Odile, Arfeuille, Chloé, Osman, Jennifer, Cassinat, Bruno, Pereira, Sabrina, Anjos-Afonso, Fernando ![]() ![]() |
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Abstract
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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences European Cancer Stem Cell Research Institute (ECSCRI) |
Publisher: | Springer Nature |
ISSN: | 0887-6924 |
Date of First Compliant Deposit: | 25 February 2020 |
Date of Acceptance: | 17 November 2019 |
Last Modified: | 30 Jun 2023 12:16 |
URI: | https://orca.cardiff.ac.uk/id/eprint/129962 |
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