TY - JOUR
T1 - Gene expression signature predicts relapse in adult patients with cytogenetically normal acute myeloid leukemia
AU - Walker, Christopher J.
AU - Mrózek, Krzysztof
AU - Ozer, Hatice Gulcin
AU - Nicolet, Deedra
AU - Kohlschmidt, Jessica
AU - Papaioannou, Dimitrios
AU - Genutis, Luke K.
AU - Bill, Marius
AU - Powell, Bayard L.
AU - Uy, Geoffrey L.
AU - Kolitz, Jonathan E.
AU - Carroll, Andrew J.
AU - Stone, Richard M.
AU - Garzon, Ramiro
AU - Byrd, John C.
AU - Eisfeld, Ann Kathrin
AU - de la Chapelle, Albert
AU - Bloomfield, Clara D.
N1 - Publisher Copyright:
© 2021 by The American Society of Hematology
PY - 2021/3/9
Y1 - 2021/3/9
N2 - Although;80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), more than half of them relapse. Better identification of patients who are likely to relapse can help to inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults with de novo CN-AML who were younger than 60 years of age and achieved a CR after induction treatment with standard “713” chemotherapy. After filtering for genes whose expressions were associated with gene mutations known to impact outcome (ie, CEBPA, NPM1, and FLT3-internal tandem duplication [FLT3-ITD]), we identified a 10-gene signature that was strongly predictive of patient relapse (area under the receiver operating characteristics curve [AUC], 0.81). The signature consisted of 7 coding genes (GAS6, PSD3, PLCB4, DEXI, JMY, NRP1, C10orf55) and 3 long noncoding RNAs. In multivariable analysis, the 10-gene signature was strongly associated with relapse (P,.001), after adjustment for the FLT3-ITD, CEBPA, and NPM1 mutational status. Validation of the expression signature in an independent patient set from The Cancer Genome Atlas showed the signature's strong predictive value, with AUC 5 0.78. Implementation of the 10-gene signature into clinical prognostic stratification could be useful for identifying patients who are likely to relapse.
AB - Although;80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), more than half of them relapse. Better identification of patients who are likely to relapse can help to inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults with de novo CN-AML who were younger than 60 years of age and achieved a CR after induction treatment with standard “713” chemotherapy. After filtering for genes whose expressions were associated with gene mutations known to impact outcome (ie, CEBPA, NPM1, and FLT3-internal tandem duplication [FLT3-ITD]), we identified a 10-gene signature that was strongly predictive of patient relapse (area under the receiver operating characteristics curve [AUC], 0.81). The signature consisted of 7 coding genes (GAS6, PSD3, PLCB4, DEXI, JMY, NRP1, C10orf55) and 3 long noncoding RNAs. In multivariable analysis, the 10-gene signature was strongly associated with relapse (P,.001), after adjustment for the FLT3-ITD, CEBPA, and NPM1 mutational status. Validation of the expression signature in an independent patient set from The Cancer Genome Atlas showed the signature's strong predictive value, with AUC 5 0.78. Implementation of the 10-gene signature into clinical prognostic stratification could be useful for identifying patients who are likely to relapse.
UR - http://www.scopus.com/inward/record.url?scp=85103626858&partnerID=8YFLogxK
U2 - 10.1182/BLOODADVANCES.2020003727
DO - 10.1182/BLOODADVANCES.2020003727
M3 - Article
C2 - 33683341
AN - SCOPUS:85103626858
SN - 2473-9529
VL - 5
SP - 1474
EP - 1482
JO - Blood Advances
JF - Blood Advances
IS - 5
ER -