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RUNX1 mutations in pediatric AML – a Japanese study

Apr 11, 2018

The clinical impact of RUNX1mutations in pediatric acute myeloid leukemia is not well understood due to the rarity of this gene. Genki Yamatofrom the National Research Institute for Child Health and Development, Tokyo, Japan, and colleagues studied the prognostic impact of RUNX1mutations in pediatric patients with de novoAML. The results of their study were reportedin a Letter to the Editor of Bloodin March 2018.

Using next-generation sequencing, the authors performed targeted deep sequencing of RUNX1in leukemic samples from 503 pediatric de novoAML patients (< 18 years) who were enrolled and treated in either the AML99 clinical trial of the Japanese Childhood AML Cooperative study (n = 134) or the AML-05 clinical trial of the Japanese Pediatric Leukemia/Lymphoma Study Group (n = 369).

RUNX1mutations were detected in 2.8% (14/503) of patients. Of these, 64% (9/14) patients had frameshift/nonsense mutations while 36% (5/14) patients had heterozygous point mutations. Three patients with mutations in the RUNX1gene reported no episode of familiar platelet disorder and thus were excluded from the final analysis which compared the outcomes of patients with or without a RUNX1mutation.

Key findings
  • 5-year overall survival in patients with (n = 11) and without (n = 492) RUNX1mutation: 30% vs72%, P< 0.001
  • 5-year event-free survival in patients with and without: 9% vs55% RUNX1mutation, P< 0.001
  • Presence of RUNX1mutations correlated with worse OS (HR = 2.572, P= 0.017) and EFS (HR = 4.351, P< 0.001)
  • Death occurred in seven patients with RUNX1mutation
  • Three of the four surviving patients underwent stem cell transplantation (SCT)

In summary, RUNX1mutations have a low frequency in pediatric AML patients and are associated with adverse outcomes.

The authors concluded by stating that “ RUNX1mutations might be a poor prognostic factor in the risk classification for pediatric AML”. They further suggested that “clinicians should consider the adaptation of SCT after first CR for patients with RUNX1mutations.”

  1. Yamato G. et al.RUNX1 mutations in pediatric acute myeloid leukemia are associated with distinct genetic features and an inferior prognosis. Blood.2018 Mar 14. DOI: 10.1182/blood-2017-11-814442. [Epub ahead of print].