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

Summary 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.