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01-02-2014 | Original Article

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

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

Published in: International Journal of Hematology | Issue 2/2014

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.

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Title: RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22)
Authors: Olfat Ismael
Akira Shimada
Shaimaa Elmahdi
Momen Elshazley
Hideki Muramatsu
Asahito Hama
Yoshiyuki Takahashi
Miho Yamada
Yuka Yamashita
Keizo Horide
Seiji Kojima
Publication date: 01-02-2014
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 2/2014
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-013-1495-5

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