title: RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22).
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.
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan, olfat_80@yahoo.com.
authors.forename: Olfat
authors.initials: O
authors.lastname: Ismael
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Shaimaa
authors.initials: S
authors.lastname: Elmahdi
authors.forename: Momen
authors.initials: M
authors.lastname: Elshazley
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Miho
authors.initials: M
authors.lastname: Yamada
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Keizo
authors.initials: K
authors.lastname: Horide
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16; D002891:Chromosomes, Human, Pair 21; D060965:Clonal Evolution; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; C493728:RUNX1 protein, human; C107302:TLS-ERG fusion protein, human