Clonal architecture and evolutionary history of Waldenström's macroglobulinemia at the single-cell level.
Dis Model Mech
; 16(8)2023 08 01.
Article
in En
| MEDLINE
| ID: mdl-37493341
ABSTRACT
To provide insight into the subclonal architecture and co-dependency patterns of the alterations in Waldenström's macroglobulinemia (WM), we performed single-cell mutational and protein profiling of eight patients. A custom panel was designed to screen for mutations and copy number alterations at the single-cell level in samples taken from patients at diagnosis (n=5) or at disease progression (n=3). Results showed that in asymptomatic WM at diagnosis, MYD88L265P was the predominant clonal alteration; other events, if present, were secondary and subclonal to MYD88L265P. In symptomatic WM, clonal diversity was more evident, uncovering combinations of alterations that synergized to promote clonal expansion and dominance. At disease progression, a dominant clone was observed, sometimes accompanied by other less complex minor clones, which could be consistent with a clonal selection process. Clonal diversity was also reduced, probably due to the effect of treatment. Finally, we combined protein expression with mutational analysis to map somatic genotype with the immunophenotype. Our findings provide a comprehensive view of the clonality of tumor populations in WM and how clonal complexity can evolve and impact disease progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Waldenstrom Macroglobulinemia
/
DNA Copy Number Variations
/
Clonal Evolution
/
Mutation
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Dis Model Mech
Journal subject:
MEDICINA
Year:
2023
Document type:
Article
Affiliation country:
Spain