High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6-RUNX1-positive acute lymphoblastic leukemia
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 represen...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 April 2019
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| In: |
Pediatric blood & cancer
Year: 2019, Volume: 66, Issue: 8 |
| ISSN: | 1545-5017 |
| DOI: | 10.1002/pbc.27780 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1002/pbc.27780
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| Author Notes: | Jana Hoffmann, Manuela Krumbholz, Helia Pimentel Gutiérrez, Marion Fillies, Annabell Szymansky, Kirsten Bleckmann, Udo Zur Stadt, Rolf Köhler, Roland P. Kuiper, Martin Horstmann, Arend von Stackelberg, Cornelia Eckert, Markus Metzler |
| Summary: | 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. |
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| Item Description: | Gesehen am 16.07.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1545-5017 |
| DOI: | 10.1002/pbc.27780 |