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Brief report
Mutational profiling of acute myeloid leukemia with normal cytogenetics in Brazilian patients: the value of next-generation sequencing for genomic classification
  1. Thiago Rodrigo de Noronha1,
  2. Miguel Mitne-Neto2,
  3. Maria de Lourdes Chauffaille1,2
  1. 1 Division of Hematology, Federal University of São Paulo, São Paulo, Brazil
  2. 2 Research and Development, Fleury Group, São Paulo, Brazil
  1. Correspondence to Thiago Rodrigo de Noronha, Division of Hematology, Federal University of São Paulo, Sao Paulo, 4037-002, Brazil; thinoronha{at}


Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients’ risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes. Every patient presented at least one mutation: DNMT3A in nine patients; IDH2 in six; IDH1 in three; NRAS and NPM1 in two; and TET2, ASXL1, PTPN11, and RUNX1 in one patient. No mutations were found in FLT3, KIT, JAK2, CEBPA, GATA2, TP53, BRAF, CBL, KRAS, and WT1 genes. Twelve patients (86%) had at least one mutation in genes related with DNA methylation (DNMT3A, IDH1, IDH2, and TET2), which is involved in regulation of gene expression and genomic stability. All patients could be reclassified based on genomic status and nine had their prognosis modified. In summary, NGS offers insights into the molecular pathogenesis and biology of cytogenetically normal AML in Brazilian patients, indicating that the prognosis could be further stratified by different mutation combinations. This study shows a different frequency of mutations in Brazilian population that should be confirmed.

  • acute myeloid leukemia
  • cytogenetically normal
  • single nucleotide polymorphism array
  • targeted next generation sequencing

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  • Contributors All authors contributed in this work.

  • Competing interests None declared.

  • Ethics approval Universidade Federal de São Paulo-UNIFESP/Hospital São Paulo, consent number 1.025.945.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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