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...
| Published in: | Pediatrics International Vol. 60; no. 1; pp. 41 - 47 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
Jan2018
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| 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 |
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