Monitoring of fusion gene transcripts to predict relapse in pediatric acute myeloid leukemia.

Abstract: Background: In acute myeloid leukemia (AML), accurate detection of minimal residual disease (MRD) enables better risk‐stratified therapy. There are few studies, however, on the monitoring of multiple fusion transcripts and evaluation of their accuracy as indicators of MRD at multiple time...

Full description

Bibliographic Details
Published in:Pediatrics International Vol. 60; no. 1; pp. 41 - 47
Main Authors: Matsuo, Hidemasa, Iijima‐Yamashita, Yuka, Yamada, Miho, Deguchi, Takao, Kiyokawa, Nobutaka, Shimada, Akira, Tawa, Akio, Tomizawa, Daisuke, Taga, Takashi, Kinoshita, Akitoshi, Adachi, Souichi, Horibe, Keizo
Format: research tables/charts Journal Article
Published: Wiley-Blackwell Jan2018
Online Access:View this record in EBSCOhost
fields @attributes:
  recordID: 1
pdfLink:
plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=127502206&site=ehost-live
header:
  @attributes:
    shortDbName: ccm
    uiTerm: 127502206
    longDbName: CINAHL Complete
    uiTag: AN
  controlInfo:
    bkinfo:
    dissinfo:
    jinfo:
      jid:
        13288067
        FS4
      jtl: Pediatrics International
      issn: 13288067
      maglogo: Y
    pubinfo:
      dt: Jan2018
      vid: 60
      iid: 1
      pid: 480
      pub: Wiley-Blackwell
      place: Malden, Massachusetts
    artinfo:
      ui:
        127502206
        127502206
        127502206
        10.1111/ped.13440
        127502206
      ppf: 41
      ppct: 6
      formats:
      tig:
        atl: Monitoring of fusion gene transcripts to predict relapse in pediatric acute myeloid leukemia.
      aug:
        au:
          Matsuo, Hidemasa
          Iijima‐Yamashita, Yuka
          Yamada, Miho
          Deguchi, Takao
          Kiyokawa, Nobutaka
          Shimada, Akira
          Tawa, Akio
          Tomizawa, Daisuke
          Taga, Takashi
          Kinoshita, Akitoshi
          Adachi, Souichi
          Horibe, Keizo
        affil: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan
      sug:
        subj:
          Leukemia, Myeloid, Acute Diagnosis
          Pediatrics
          RNA
          Biological Markers
          Human
          Polymerase Chain Reaction Methods
          Gene Expression
          Retrospective Design
      ab: Abstract: Background: In acute myeloid leukemia (AML), accurate detection of minimal residual disease (MRD) enables better risk‐stratified therapy. There are few studies, however, on the monitoring of multiple fusion transcripts and evaluation of their accuracy as indicators of MRD at multiple time points. Methods: We retrospectively examined RNA obtained from 82 pediatric AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML‐05 study. The expression of six important fusion transcripts (<italic>AML1(RUNX1)‐ETO</italic>,<italic> CBFB‐MYH11</italic>,<italic> MLL(KMT2A)‐AF9</italic>,<italic> MLL‐ELL</italic>,<italic> MLL‐AF6</italic>, and <italic>FUS‐ERG</italic>) was analyzed at five time points 30–40 days apart following diagnosis. Results: In patients with <italic>AML1‐ETO</italic> (n = 36 at time point 5), all six patients with >3,000 copies and four of 30 patients with ≤3,000 copies relapsed. <italic>AML1‐ETO</italic> transcripts persisted during treatment even in patients without relapse, as well as <italic>CBFB‐MYH11</italic> transcripts. In contrast, in patients with <italic>MLL‐AF9</italic> (n = 9 at time point 5), two patients were positive for <italic>MLL‐AF9</italic> expression (>50 copies) and both relapsed. Only one of seven <italic>MLL‐AF9</italic>‐negative patients relapsed. In the <italic>AML1‐ETO</italic> group, MRD‐positive patients (>3,000 copies at time point 5) had significantly lower relapse‐free survival (RFS;<italic> P </italic><<italic> </italic>0.0001) and overall survival (OS;<italic> P </italic>=<italic> </italic>0.009) than MRD‐negative patients. Similarly, in the <italic>MLL‐AF9</italic> group, MRD‐positive patients (>50 copies at time point 5) had significantly lower RFS (<italic>P </italic>=<italic> </italic>0.002) and OS (<italic>P </italic>=<italic> </italic>0.002) than MRD‐negative patients. Conclusions: Detection of <italic>MLL‐AF9</italic> transcripts on real‐time quantitative polymerase chain reaction is a promising marker of relapse in pediatric AML. In contrast, the clinical utility of detecting <italic>AML1‐ETO</italic> and <italic>CBFB‐MYH11</italic> expression is limited, although higher <italic>AML1‐ETO</italic> expression can be a potential predictor of relapse when assessed according to an optimal threshold.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
    refInfo:
    holdings:
      @attributes:
        islocal: N