Myelodysplastic syndromes with 20q deletion: incidence, prognostic value and impact on response to azacitidine of ASXL1 chromosomal deletion and genetic mutations
Por:
Martin, I, Villamon, E, Abellan, R, Calasanz, MJ, Irigoyen, A, Sanz, G, Such, E, Mora, E, Gutierrez, M, Collado, R, Garcia-Serra, R, Vara, M, Blanco, ML, Oiartzabal, I, Alvarez, S, Bernal, T, Granada, I, Xicoy, B, Jerez, A, Calabuig, M, Diez, R, Gil, A, Diez-Campelo, M, Solano, C, Tormo, M
Publicada:
1 ago 2021
Ahead of Print:
1 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 center dot 5%): 34 patients (22%) with a gene deletion (ASXL1(DEL)) and 10 patients (6 center dot 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 center dot 84; 95% confidence interval, (CI): 1 center dot 11-3 center dot 04; P = 0 center dot 018] and a higher rate for acute myeloid leukaemia progression (HR 2 center dot 47; 95% CI: 1 center dot 07-5 center dot 70, P = 0 center dot 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:
Martin, I:
Univ Valencia, Hosp Clin Univ Valencia, INCLIVA Res Inst, Dept Hematol, Valencia, Spain
Villamon, E:
Univ Valencia, Hosp Clin Univ Valencia, INCLIVA Res Inst, Dept Hematol, Valencia, Spain
Abellan, R:
Hosp Clin Univ Valencia, INCLIVA Res Inst, Biochem & Mol Pathol Dept, Valencia, Spain
Calasanz, MJ:
Univ Navarra, CMA LAB Diagnost, Pamplona, Spain
Irigoyen, A:
Univ Navarra, CMA LAB Diagnost, Pamplona, Spain
Sanz, G:
Hosp Univ & Politecn La Fe, Hlth Res Inst Hosp La Fe, Dept Hematol, Valencia, Spain
Such, E:
Hosp Univ & Politecn La Fe, Hlth Res Inst Hosp La Fe, Dept Hematol, Valencia, Spain
Mora, E:
Hosp Univ & Politecn La Fe, Hlth Res Inst Hosp La Fe, Dept Hematol, Valencia, Spain
Gutierrez, M:
Hosp Univ Infanta Sofia, Dept Genet, Madrid, Spain
Collado, R:
Consorcio Hosp Gen Univ Valencia, Res Fdn Gen Univ Hosp Valencia, Dept Hematol, Valencia, Spain
Garcia-Serra, R:
Consorcio Hosp Gen Univ Valencia, Res Fdn Gen Univ Hosp Valencia, Dept Hematol, Valencia, Spain
Vara, M:
Hosp Univ Cruces, Dept Hematol, Baracaldo, Spain
Blanco, ML:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain
Oiartzabal, I:
Hosp Txagorritxu, Dept Hematol, Vitoria, Spain
Alvarez, S:
NIM Genet, Genom & Med, Madrid, Spain
Hosp HM Sanchinarro, Dept Hematol, Madrid, Spain
Bernal, T:
Hosp Univ Asturias, IISPA, IUOPA, Dept Hematol, Oviedo, Spain
Granada, I:
Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Inst Catala Oncol, Josep Carreras Leukaemia Res Inst,Dept Hematol, Barcelona, Spain
Xicoy, B:
Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Inst Catala Oncol, Josep Carreras Leukaemia Res Inst,Dept Hematol, Barcelona, Spain
Jerez, A:
Hosp Univ Morales Meseguer, Dept Hematol, Murcia, Spain
Calabuig, M:
Univ Valencia, Hosp Clin Univ Valencia, INCLIVA Res Inst, Dept Hematol, Valencia, Spain
Diez, R:
Hosp Univ Miguel Servet Zaragoza, Dept Hematol, Zaragoza, Spain
Gil, A:
Hosp Univ Guadalajara, Dept Hematol, Guadalajara, Spain
Diez-Campelo, M:
Hosp Univ Salamanca, Dept Hematol, Salamanca, Spain
Solano, C:
Univ Valencia, Hosp Clin Univ Valencia, INCLIVA Res Inst, Dept Hematol, Valencia, Spain
Univ Valencia, Sch Med, Dept Med, Valencia, Spain
Tormo, M:
Univ Valencia, Hosp Clin Univ Valencia, INCLIVA Res Inst, Dept Hematol, Valencia, Spain
|