RT Journal Article
T1 Monitoring of clonal evolution of acute myeloid leukemia identifies the leukemia subtype, clinical outcome and potential new drug targets for post-remission strategies or relapse
A1 Onecha, Esther
A1 Rapado, Inmaculada
A1 Morales, Maria Luz
A1 Carreño-Tarragona, Gonzalo
A1 Martínez-Sánchez, Pilar
A1 Gutiérrez, Xavier
A1 Sánchez Pina, José María
A1 Linares Gómez, María
A1 Gallardo, Miguel
A1 Martínez López, Joaquín
A1 Ayala Díaz, Rosa María
AB In cases of treatment failure in acute myeloid leukemia (AML), the utility of mutational profiling in primary refractoriness and relapse is not established. We undertook a perspective study using next-generation sequencing (NGS) of clinical follow-up samples (n=91) from 23 patients with AML with therapeutic failure to cytarabine plus idarubicin or fludarabine. Cases of primary refractoriness to treatment were associated with a lower number of DNA variants at diagnosis than cases of relapse (median 1.67 and 3.21, respectively, p=0.029). The most frequently affected pathways in patients with primary refractoriness were signaling, transcription and tumor suppression, whereas methylation and splicing pathways were mainly implicated in relapsed patients. New therapeutic targets, either by an approved drug or within clinical trials, were not identified in any of the cases of refractoriness (0/10); however, 8 potential new targets were found in 5 relapsed patients (5/13) (p=0.027): 1 IDH2, 3 SF3B1, 2 KRAS, 1 KIT and 1 JAK2.  Sixty-five percent of all variants detected at diagnosis were not detected at complete response (CR). Specifically, 100% of variants in EZH2, RUNX1, VHL, FLT3, ETV6, U2AF1, PHF6 and SF3B1 disappeared at CR, indicating their potential use as markers to evaluate minimal residual disease (MRD) for follow-up of AML.  Molecular follow-up using a custom NGS myeloid panel of 32 genes in the post-treatment evaluation of AML can help in the stratification of prognostic risk, the selection of MRD markers to monitor the response to treatment and guide post-remission strategies targeting AML, and the selection of new drugs for leukemia relapse.
SN 1592-8721
SN 0390-6078
YR 2020
FD 2020-07-30
LK https://hdl.handle.net/20.500.14352/101837
UL https://hdl.handle.net/20.500.14352/101837
LA eng
NO Instituto de Salud Carlos III
NO CRIS against Cancer foundation
NO Spanish Ministry of Economy and Competitiveness
DS Docta Complutense
RD 10 abr 2025