Genetic biomarkers identify a subgroup of high-risk patients within low-risk NPM1-mutated acute myeloid leukemia

Abstract

Although acute myeloid leukemia (AML) with NPM1^mut/FLT3-ITD^neg is a low-risk entity, its relapse rate remains high. Out of 333 AML patients, 27 were NPM1^mut, and were analyzed in greater detail in order to find associations between clinical and molecular features and cumulative incidence of relapse. Next-generation sequencing (NGS) was performed on diagnosis and remission samples using two capture-based panels. The presence of the FLT3^D835 variant at diagnosis and a qPCR value of NPM1^mut ≥0.1% after induction chemotherapy were associated with an increased probability of relapse, especially if both conditions are present together. By contrast, patients in which the main clone found at diagnosis harbored NPM1 variant had a lower risk of relapse. Nineteen of the 85 variants found at diagnosis were detected by NGS in remission. AML Subgroup with NPM1^mut/FLT3-ITD^neg is a heterogeneous entity, which can be further risk-stratified based on molecular biomarkers.

Keywords:

• Acute myeloid leukemia
• NPM1
• FLT3
• genetic biomarkers
• prognostic impact

Acknowledgements

The authors thank Ms Pilar Martin for her revision of the paper.

Ethics approval and consent to participate

The ethics committee of the Gregorio Marañón General University Hospital approved the study and all patients signed the informed consent document.

Disclosure statement

Julia Suárez-González, Ismael Buño and Carolina Martínez-Laperche collaborated in the design of the panel LMA-GeneSGKit (Sistemas Genómicos, Spain).

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Fundación Mutua Madrileña under Grant FMM15-04; and Instituto de Salud Carlos III under Grant PI17/1880 (Ministry of Science and Innovation, Spain), co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”.