Myelodysplastic syndromes with 20q deletion: incidence, prognostic value and impact on response to azacitidine of ASXL1 chromosomal deletion and genetic mutations.
Br J Haematol
; 194(4): 708-717, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34296432
ABSTRACT
In myelodysplastic syndromes (MDS), the 20q deletion [del(20q)] may cause deletion of the ASXL1 gene. We studied 153 patients with MDS and del(20q) to assess the incidence, prognostic value and impact on response to azacitidine (AZA) of ASXL1 chromosomal alterations and genetic mutations. Additionally, in vitro assay of the response to AZA in HAP1 (HAP1WT ) and HAP1 ASXL1 knockout (HAP1KN ) cells was performed. ASXL1 chromosomal alterations were detected in 44 patients (28·5%) 34 patients (22%) with a gene deletion (ASXL1DEL ) and 10 patients (6·5%) with additional gene copies. ASXL1DEL was associated with a lower platelet count. The most frequently mutated genes were U2AF1 (16%), ASXL1 (14%), SF3B1 (11%), TP53 (7%) and SRSF2 (6%). ASXL1 alteration due to chromosomal deletion or genetic mutation (ASXL1DEL /ASXL1MUT ) was linked by multivariable analysis with shorter overall survival [hazard ratio, (HR) 1·84; 95% confidence interval, (CI) 1·11-3·04; P = 0·018] and a higher rate for acute myeloid leukaemia progression (HR 2·47; 95% CI 1·07-5·70, P = 0·034). ASXL1DEL /ASXL1MUT patients were correlated by univariable analysis with a worse response to AZA. HAP1KN cells showed more resistance to AZA compared to HAP1WT cells. In conclusion, ASXL1 alteration exerts a negative impact on MDS with del(20q) and could become useful for prognostic risk stratification and treatment decisions.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Azacitidina
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Síndromes Mielodisplásicas
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Deleção Cromossômica
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Antimetabólitos Antineoplásicos
Tipo de estudo:
Diagnostic_studies
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Incidence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Espanha