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. 2023 Jun;201(6):1144-1152.
doi: 10.1111/bjh.18800. Epub 2023 Apr 17.

Subclinical minute FLT3-ITD clone can be detected in clinically FLT3-ITD-negative acute myeloid leukaemia at diagnosis

Shota Yokoyama  1 , Masahiro Onozawa  1 , Shota Yoshida  1 , Naoki Miyashita  1 , Hiroyuki Kimura  1 , Shogo Takahashi  1 , Toshihiro Matsukawa  1 , Hideki Goto  1   2 , Shinichi Fujisawa  2 , Kosuke Miki  3 , Daisuke Hidaka  4 , Junichi Hashiguchi  5 , Kentaro Wakasa  6 , Makoto Ibata  7 , Yukari Takeda  8 , Akio Shigematsu  9 , Katsuya Fujimoto  10 , Yutaka Tsutsumi  11 , Akio Mori  12 , Toshimichi Ishihara  13 , Yasutaka Kakinoki  14 , Takeshi Kondo  12 , Daigo Hashimoto  1 , Takanori Teshima  1   2
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Free article

Subclinical minute FLT3-ITD clone can be detected in clinically FLT3-ITD-negative acute myeloid leukaemia at diagnosis

Shota Yokoyama et al. Br J Haematol. 2023 Jun.
Free article

Abstract

Recent advances in next-generation sequencing (NGS) have enabled the detection of subclinical minute FLT3-ITD. We selected 74 newly diagnosed, cytogenetically normal acute myeloid leukaemia (AML) samples in which FLT3-ITD was not detected by gel electrophoresis. We sequenced them using NGS and found minute FLT3-ITDs in 19 cases. We compared cases with clinically relevant FLT3-ITD (n = 37), cases with minute FLT3-ITD (n = 19) and cases without detectable FLT3-ITD (n = 55). Molecular characteristics (location and length) of minute FLT3-ITD were similar to those of clinically relevant FLT3-ITD. Survival of cases with minute FLT3-ITD was similar to that of cases without detectable FLT3-ITD, whereas the relapse rate within 1 year after onset was significantly higher in cases with minute FLT3-ITD. We followed 18 relapsed samples of cases with clinically FLT3-ITD-negative at diagnosis. Two of 3 cases with minute FLT3-ITD relapsed with progression to clinically relevant FLT3-ITD. Two of 15 cases in which FLT3-ITD was not detected by NGS relapsed with the emergence of minute FLT3-ITD, and one of them showed progression to clinically relevant FLT3-ITD at the second relapse. We revealed the clonal dynamics of subclinical minute FLT3-ITD in clinically FLT3-ITD-negative AML. Minute FLT3-ITD at the initial AML can expand to become a dominant clone at relapse.

Keywords: Hokkaido Leukemia Net (HLN); acute myeloid leukaemia (AML); clonal diversity; minute FLT3-ITD; next-generation sequencing (NGS); relapse.

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