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

Olfat Ismael, Akira Shimada, Shaimaa Elmahdi, Momen Elshazley, Hideki Muramatsu, Asahito Hama, Yoshiyuki Takahashi, Miho Yamada, Yuka Yamashita, Keizo Horide, Seiji Kojima

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalInternational journal of hematology
Volume99
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • AML
  • RUNX1
  • TLS/FUS-ERG
  • Translocation

ASJC Scopus subject areas

  • Hematology

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    Ismael, O., Shimada, A., Elmahdi, S., Elshazley, M., Muramatsu, H., Hama, A., Takahashi, Y., Yamada, M., Yamashita, Y., Horide, K., & Kojima, S. (2014). RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22). International journal of hematology, 99(2), 169-174. https://doi.org/10.1007/s12185-013-1495-5