Myelodysplastic syndromes with 20q deletion: incidence, prognostic value and impact on response to azacitidine of ASXL1 chromosomal deletion and genetic mutations.
Por:
Martín I, Villamón E, Abellán R, Calasanz MJ, Irigoyen A, Sanz G, Such E, Mora E, Gutiérrez M, Collado R, García-Serra R, Vara M, Blanco ML, Oiartzabal I, Álvarez S, Bernal T, Granada I, Xicoy B, Jerez A, Calabuig M, Diez R, Gil Á, Díez-Campelo M, Solano C, Tormo M
Publicada:
1 ago 2021
Ahead of Print:
22 jul 2021
Resumen:
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 (HAP1(WT) ) and HAP1 ASXL1 knockout (HAP1(KN) ) cells was performed. ASXL1 chromosomal alterations were detected in 44 patients (28·5%): 34 patients (22%) with a gene deletion (ASXL1(DEL) ) and 10 patients (6·5%) with additional gene copies. ASXL1(DEL) 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 (ASXL1(DEL) /ASXL1(MUT) ) 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). ASXL1(DEL) /ASXL1(MUT) patients were correlated by univariable analysis with a worse response to AZA. HAP1(KN) cells showed more resistance to AZA compared to HAP1(WT) 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.
Filiaciones:
Martín I:
Hematology Department, Hospital Clínico Universitario de Valencia, INCLIVA Research Institute, University of Valencia, Valencia, Spain
Villamón E:
Hematology Department, Hospital Clínico Universitario de Valencia, INCLIVA Research Institute, University of Valencia, Valencia, Spain
Abellán R:
Biochemistry and Molecular Pathology Department, Hospital Clínico Universitario de Valencia, INCLIVA Research Institute, Valencia, Spain
Calasanz MJ:
CIMA LAB Diagnostics, Universidad de Navarra, Pamplona, Spain
Irigoyen A:
CIMA LAB Diagnostics, Universidad de Navarra, Pamplona, Spain
Sanz G:
Hematology Department, Hospital Universitario y Politécnico La Fe, Health Research Institute Hospital La Fe, IIS La Fe, Valencia, Spain
Such E:
Hematology Department, Hospital Universitario y Politécnico La Fe, Health Research Institute Hospital La Fe, IIS La Fe, Valencia, Spain
Mora E:
Hematology Department, Hospital Universitario y Politécnico La Fe, Health Research Institute Hospital La Fe, IIS La Fe, Valencia, Spain
Gutiérrez M:
Genetics Department, Hospital Universitario Infanta Sofía, Madrid, Spain
Collado R:
Hematology Department, Consorcio Hospital General Universitario de Valencia, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
García-Serra R:
Hematology Department, Consorcio Hospital General Universitario de Valencia, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Vara M:
Hematology Department, Hospital Universitario de Cruces, Barakaldo, Spain
Blanco ML:
Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Oiartzabal I:
Hematology Department, Hospital de Txagorritxu, Vitoria-Gasteiz, Spain
Álvarez S:
NIMGenetics, Genómica y Medicina, Madrid, Spain
Hematology Department, Hospital HM Sanchinarro, Madrid, Spain
Bernal T:
Hematology Department, Hospital Universidad de Asturias, IISPA, IUOPA, Oviedo, Spain
Granada I:
Hematology Department, Hospital Germans Trias i Pujol, Institut Català d'Oncologia, Josep Carreras Leukaemia Research Institute (IJC), Universidad Autónoma de Barcelona, Barcelona, Spain
Xicoy B:
Hematology Department, Hospital Germans Trias i Pujol, Institut Català d'Oncologia, Josep Carreras Leukaemia Research Institute (IJC), Universidad Autónoma de Barcelona, Barcelona, Spain
Jerez A:
Hematology Department, Hospital Universitario Morales Meseguer, Murcia, Spain
Calabuig M:
Hematology Department, Hospital Clínico Universitario de Valencia, INCLIVA Research Institute, University of Valencia, Valencia, Spain
Diez R:
Hematology Department, Hospital Universitario Miguel Servet de Zaragoza, Zaragoza, Spain
Gil Á:
Hematology Department, Hospital Universitario de Guadalajara, Guadalajara, Spain
Díez-Campelo M:
Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain
Solano C:
Hematology Department, Hospital Clínico Universitario de Valencia, INCLIVA Research Institute, University of Valencia, Valencia, Spain
Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain
Tormo M:
Hematology Department, Hospital Clínico Universitario de Valencia, INCLIVA Research Institute, University of Valencia, Valencia, Spain
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