Hoffmann J, Krumbholz M, Gutiérrez HP, Fillies M, Szymansky A, Bleckmann K, zur Stadt U, Köhler R, Kuiper RP, Horstmann M, von Stackelberg A, Eckert C, Metzler M (2019)
Publication Type: Journal article
Publication year: 2019
Article Number: e27780
DOI: 10.1002/pbc.27780
Background: Assessment of minimal residual disease (MRD) is an integral component for response monitoring and treatment stratification in acute lymphoblastic leukemia (ALL). We aimed to evaluate the genomic ETV6-RUNX1 fusion sites as a single marker for MRD quantification. Procedure: In a representative, uniformly treated cohort of pediatric relapsed ALL patients (n = 52), ETV6-RUNX1 fusion sites were compared to the current gold standard, immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements. Results: Primer/probe sets designed to ETV6-RUNX1 fusions achieved significantly more frequent a sensitivity and a quantitative range of at least 10 –4 compared to the gold standard with 100% and 73% versus 76% and 47%, respectively. The breakpoint sequence was identical at diagnosis and relapse in all tested cases. There was a high degree of concordance between quantitative MRD results assessed using ETV6-RUNX1 and the highest Ig/TCR marker (Spearman's 0.899, P <.01) with differences >½ log-step in only 6% of patients. A high proportion of ETV6-RUNX1-positive ALL relapses (40%) in our cohort showed a poor response to induction treatment at relapse, and therefore had an indication for hematopoietic stem cell transplantation, demonstrating the need of accurate identification of this subgroup. Conclusions: ETV6-RUNX1 fusion sites are highly sensitive and reliable MRD markers. Our data confirm that they are unaffected by clonal evolution and selection during front-line and second-line chemotherapy in contrast to Ig/TCR rearrangements, which require several markers per patient to compensate for the observed loss of target clones. In future studies, the genomic ETV6-RUNX1 fusion can be used as single MRD marker.
APA:
Hoffmann, J., Krumbholz, M., Gutiérrez, H.P., Fillies, M., Szymansky, A., Bleckmann, K.,... Metzler, M. (2019). High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6-RUNX1-positive acute lymphoblastic leukemia. Pediatric Blood & Cancer. https://doi.org/10.1002/pbc.27780
MLA:
Hoffmann, Jana, et al. "High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6-RUNX1-positive acute lymphoblastic leukemia." Pediatric Blood & Cancer (2019).
BibTeX: Download