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- Title
Monitoring of fusion gene transcripts to predict relapse in pediatric acute myeloid leukemia.
- 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
- Abstract
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.
- Subjects
ACUTE myeloid leukemia diagnosis; BIOMARKERS; GENE expression; PEDIATRICS; POLYMERASE chain reaction; RNA; RETROSPECTIVE studies
- Publication
Pediatrics International, 2018, Vol 60, Issue 1, p41
- ISSN
1328-8067
- Publication type
Article
- DOI
10.1111/ped.13440