International Journal of Hematology

, Volume 99, Issue 2, pp 169–174 | Cite as

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
Original Article
First Online:
Received:
Revised:
Accepted:

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.

Keywords

RUNX1 AML Translocation TLS/FUS-ERG 
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Notes

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© The Japanese Society of Hematology 2013

Authors and Affiliations

  • Olfat Ismael
    • 1
    • 2
  • Akira Shimada
    • 1
    • 3
    • 4
  • Shaimaa Elmahdi
    • 1
  • Momen Elshazley
    • 5
    • 6
  • Hideki Muramatsu
    • 1
  • Asahito Hama
    • 1
  • Yoshiyuki Takahashi
    • 1
  • Miho Yamada
    • 3
  • Yuka Yamashita
    • 3
  • Keizo Horide
    • 3
  • Seiji Kojima
    • 1
  1. 1.Department of PediatricsNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Pediatrics, EL-Hilal HospitalGeneral Authority for Health InsuranceSohagEgypt
  3. 3.Clinical Research Center, National Hospital OrganizationNagoya Medical CenterNagoyaJapan
  4. 4.Department of PediatricsOkayama University HospitalOkayamaJapan
  5. 5.Department of Respiratory MedicineNagoya University Graduate School of MedicineNagoyaJapan
  6. 6.Industrial Medicine and Occupational Diseases Unit, Faculty of MedicineSohag UniversitySohagEgypt

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