title: Minimal residual disease monitoring in t(8;21) acute myeloid leukemia based on RUNX1-RUNX1T1 fusion quantification on genomic DNA.
abstract: Although acute myeloid leukemia (AML) with t(8;21) belongs to the favorable risk AML subset, relapse incidence may reach 30% in those patients. RUNX1-RUNX1T1 fusion transcript is a well-established marker for minimal residual disease (MRD) monitoring. In this study, we investigated the feasibility and performances of RUNX1-RUNX1T1 DNA as MRD marker in AML with t(8;21). In 17/22 patients with t(8;21)-positive AML treated in the French CBF-2006 trial, breakpoints in RUNX1 and RUNX1T1 were identified using long-range PCR followed by next-generation sequencing. RUNX1-RUNX1T1 DNA quantification was performed by real-time quantitative PCR using patient-specific primers and probe. MRD levels were evaluated in 71 follow-up samples from 16 patients, with a median of four samples [range 2-7] per patient. RUNX1 breakpoints were located in intron 5 in all cases. RUNX1T1 breakpoints were located in intron 1b in 15 cases and in intron 1a in two cases. RUNX1-RUNX1T1 MRD levels measured on DNA and RNA were strongly correlated (r = 0.8, P < 0.0001). Discordant MRD results were observed in 10/71 (14%) of the samples: in three samples from two patients who relapsed, RUNX1-RUNX1T1 was detectable only on DNA, while RUNX1-RUNX1T1 was detectable only on RNA in seven samples. MRD monitoring on genomic DNA is feasible, but with sensitivity variations depending on the patient breakpoint sequence and the qPCR assay efficiency. Although interpretation of the results is easier because it is closely related to the number of leukemic cells, this method greatly increases time, cost and complexity, which limits its interest in routine practice.
authors.affiliation: Laboratory of Hematology, Biology and Pathology Center, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Duployez
authors.forename: Olivier
authors.initials: O
authors.lastname: Nibourel
authors.forename: Alice
authors.initials: A
authors.lastname: Marceau-Renaut
authors.forename: Christophe
authors.initials: C
authors.lastname: Willekens
authors.forename: Nathalie
authors.initials: N
authors.lastname: Helevaut
authors.forename: Aurélie
authors.initials: A
authors.lastname: Caillault
authors.forename: Céline
authors.initials: C
authors.lastname: Villenet
authors.forename: Karine
authors.initials: K
authors.lastname: Celli-Lebras
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boissel
authors.forename: Eric
authors.initials: E
authors.lastname: Jourdan
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
mesh_terms: D000293:Adolescent; D000328:Adult; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D023281:Genomics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein