PuSH - Publikationsserver des Helmholtz Zentrums München

Schnittger, S.* ; Eder, C.* ; Jeromin, S.* ; Alpermann, T.* ; Fasan, A.* ; Grossmann, V.* ; Kohlmann, A.* ; Illig, T. ; Klopp, N. ; Wichmann, H.-E. ; Kreuzer, K.A.* ; Schmid, C.* ; Staib, P.* ; Peceny, R.* ; Schmitz, N.* ; Kern, W.* ; Haferlach, C.* ; Haferlach, T.*

ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome.

Leukemia 27, 82-91 (2013)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
We aimed at evaluating ASXL1mut in 740 AML with intermediate risk karyotype for frequency, association with other mutations and impact on outcome. Five hundred fifty-three cases had a normal karyotype (NK) and 187 had intermediate risk aberrant cytogenetics. Overall, ASXL1mut were detected in 127/740 patients (17.2%). ASXL1mut were more frequent in males than in females (23.5% vs 9.9%, P<0.001). They were associated with higher age (median: 71.8 vs 61.8, P<0.001), a history of preceding myelodysplastic syndromes, and with a more immature immunophenotype compared with patients with wild-type ASXL1 (ASXL1wt). ASXL1mut were more frequent in patients with aberrant karyotype (58/187; 31.0%), especially in cases with trisomy 8 (39/74; 52.7%), than in those with NK (69/553; 12.5%; P<0.001). ASXL1mut were observed more frequent in RUNX1mut (P<0.001), and less frequent in NPM1mut (P<0.001), FLT3-internal tandem duplication (ITD) (P<0.001), FLT3-TKD (P = 0.001) and DNMT3Amut (P<0.001). Patients with ASXL1mut had a shorter overall survival (OS) (P<0.001) and event free survival (P = 0.012) compared with ASXL1wt. In multivariable analysis, ASXL1mut was an independent adverse factor for OS (P = 0.032, relative risk: 1.70). In conclusion, ASXL1mut belong to the most frequent mutations in intermediate risk group AML. Their strong and independent dismal prognostic impact suggests the inclusion into the diagnostic work-up of AML. Leukemia (2013) 27, 82-91; doi:10.1038/leu.2012.262
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Asxl1 Mutations ; Aml ; Prognosis ; Intermediate Karyotype; Acute Myeloid-leukemia ; Chronic Myelomonocytic Leukemia ; Minimal Residual Disease ; Myeloproliferative Neoplasms ; Myelodysplastic Syndromes ; Prognostic-significance ; Sequencing Technology ; Unselected Patients ; Poor-prognosis ; Gene Asxl1
ISSN (print) / ISBN 0887-6924
e-ISSN 1476-5551
Zeitschrift Leukemia
Quellenangaben Band: 27, Heft: 1, Seiten: 82-91 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Molecular Epidemiology (AME)
Institute of Epidemiology (EPI)