MRD-quantification during treatment of ETV6-RUNX1 positive ALL relapses using the genomic breakpoint of the fusion gene

T-cell receptor (TCR)/Immunoglobulin(IG)-gene rearrangements used as minimal residual disease (MRD) markers in acute lymphoblastic leukaemia (ALL) can describe different subclones at initial/relapse diagnosis because leukaemic clones are exposed to influences of clonal evolution and selection during/after treatment.

We aimed at investigating whether the genomic breakpoint of the fusion gene ETV6-RUNX1 (E/R) is a suitable MRD-marker.

Patients with an E/R positive first ALL relapse were included in the study (n=76). Identification and sequencing of the breakpoint was performed using nested multiplex long-range PCR. Clone specific primer/probe sets were designed, tested, and used for MRD-quantification (n=279 samples).

In 91% of patients (43/47) a sensitivity of 1E-04/-05 was reached. The quantitative data correlated well with the TCR/IG-results (>1/2 log-step difference in 34/279). The genomic breakpoint sequence was identical between different disease stages.

The genomic breakpoint of the fusion gene reveals as a very sensitive, stable MRD-marker and is therefore excellently suitable for MRD-quantification in E/R positive ALL.