Gene expression signature predicts relapse in adult patients with cytogenetically normal acute myeloid leukemia

Christopher J. Walker, Krzysztof Mrózek, Hatice Gulcin Ozer, Deedra Nicolet, Jessica Kohlschmidt, Dimitrios Papaioannou, Luke K. Genutis, Marius Bill, Bayard L. Powell, Geoffrey L. Uy, Jonathan E. Kolitz, Andrew J. Carroll, Richard M. Stone, Ramiro Garzon, John C. Byrd, Ann Kathrin Eisfeld, Albert de la Chapelle, Clara D. Bloomfield

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1474-1482
Number of pages9
JournalBlood Advances
Volume5
Issue number5
DOIs
StatePublished - Mar 9 2021

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