Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes.
Leukemia
; 38(9): 1992-2002, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39033241
ABSTRACT
Mutations in the cohesin complex components (STAG2, RAD21, SMC1A, SMC3, and PDS5B) are recurrent genetic drivers in myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Whether the different cohesin subunit mutations share clinical characteristics and prognostic significance is not known. We analyzed 790 cohesin-mutant patients from the Dana-Farber Cancer Institute (DFCI) and the Munich Leukemia Laboratory (MLL), 390 of which had available outcome data, and identified subunit-specific clinical, prognostic, and genetic characteristics suggestive of distinct ontogenies. We found that STAG2 mutations are acquired at MDS stage and are associated with secondary AML, adverse prognosis, and co-occurrence of secondary AML-type mutations. In contrast, mutations in RAD21, SMC1A and SMC3 share features with de novo AML with better prognosis, and co-occurrence with de novo AML-type lesions. The findings show the heterogeneous nature of cohesin complex mutations, and inform clinical and prognostic classification, as well as distinct biology of the cohesin complex.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Síndromes Mielodisplásicos
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Proteínas Cromosómicas no Histona
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Leucemia Mieloide Aguda
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Proteínas de Ciclo Celular
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Cohesinas
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Mutación
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article