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Gene Expression Signature Predicts Relapse in Adult Patients with Cytogenetically Normal Acute Myeloid Leukemia

ABSTRACT: Although approximately 80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), over half of them relapse. Better identification of patients who are likely to relapse can help inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults with de novo CN-AML younger than 60 years who achieved a CR after induction treatment with standard “7+3” chemotherapy. After filtering for genes whose expressions were associated with gene mutations known to impact on outcome (i.e., CEBPA, NPM1, and FLT3-internal tandem duplication [FLT3-ITD]), we identified a 10-gene signature strongly predictive of patient relapse (area under the curve [AUC]=0.81). The signature consisted of seven coding genes: GAS6, PSD3, PLCB4, DEXI, JMY, NRP1, C10orf55, and three long non-coding 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=0.78. Implementation of the 10-gene signature into clinical prognostic stratification could be useful for identifying patients likely to relapse.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165430 | GEO | 2021/03/16

REPOSITORIES: GEO

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