RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22)

Int J Hematol. 2014 Feb;99(2):169-74. doi: 10.1007/s12185-013-1495-5. Epub 2013 Dec 28.

Abstract

TLS/FUS-ERG chimeric fusion transcript resulting from translocation changes involving chromosomes 16 and 21 is a rare genetic event associated with acute myeloid leukemia (AML). The distinct t(16;21) AML subtype exhibits unique clinical and morphological features and is associated with poor prognosis and a high relapse rate; however, the underlying mechanism remains to be clarified. Recently, whole-genome sequencing revealed a large set of genetic alterations that may be relevant for the dynamic clonal evolution and relapse pathogenesis of AML. Here, we report three pediatric AML patients with t(16;21) (p11; q22). The TLS/FUS-ERG fusion transcript was detected in all diagnostic and relapsed samples, with the exception of one relapsed sample. We searched for several genetic lesions, such as RUNX1, FLT3, c-KIT, NRAS, KRAS, TP53, CBL, ASXL1, IDH1/2, and DNMT3A, in primary and relapsed AML samples. Interestingly, we found RUNX1 mutation in relapsed sample of one patient in whom cytogenetic analysis showed the emergence of a new additional clone. Otherwise, there were no genetic alterations in FLT3, c-KIT, NRAS, KRAS, TP53, CBL, ASXL1, IDH1/2, or DNMT3A. Our results suggest that precedent genetic alterations may be essential to drive the progression and relapse of t(16;21)-AML patients.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 16
  • Chromosomes, Human, Pair 21
  • Clonal Evolution*
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism
  • Recurrence
  • Translocation, Genetic*
  • Treatment Outcome

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • RNA-Binding Protein FUS
  • RUNX1 protein, human
  • TLS-ERG fusion protein, human