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

Fingerprint

Clonal Evolution
Acute Myeloid Leukemia
Pediatrics
Mutation
Recurrence
Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 21
Cytogenetic Analysis
Clone Cells
Genome

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22). / Ismael, Olfat; Shimada, Akira; Elmahdi, Shaimaa; Elshazley, Momen; Muramatsu, Hideki; Hama, Asahito; Takahashi, Yoshiyuki; Yamada, Miho; Yamashita, Yuka; Horide, Keizo; Kojima, Seiji.

In: International Journal of Hematology, Vol. 99, No. 2, 02.2014, p. 169-174.

Research output: Contribution to journalArticle

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, vol. 99, no. 2, pp. 169-174. https://doi.org/10.1007/s12185-013-1495-5
Ismael, Olfat ; Shimada, Akira ; Elmahdi, Shaimaa ; Elshazley, Momen ; Muramatsu, Hideki ; Hama, Asahito ; Takahashi, Yoshiyuki ; Yamada, Miho ; Yamashita, Yuka ; Horide, Keizo ; Kojima, Seiji. / RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22). In: International Journal of Hematology. 2014 ; Vol. 99, No. 2. pp. 169-174.
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