title: Relapse kinetics in acute myeloid leukaemias with MLL translocations or partial tandem duplications within the MLL gene.
abstract: Correct action upon re-emergence of minimal residual disease in acute myeloid leukaemia (AML) patients has not yet been established. The applicability of demethylating agents and use of allogeneic stem cell transplantation will be dependent on pre-relapse AML growth rates. We here delineate molecular growth kinetics of AML harbouring MLL partial tandem duplication (MLL-PTD; 37 cases) compared to those harbouring MLL translocations (43 cases). The kinetics of MLL-PTD relapses was both significantly slower than those of MLL translocation positive ones (median doubling time: MLL-PTD: 24 d, MLL-translocations: 12 d, P = 0·015, Wilcoxon rank sum test), and displayed greater variation depending on additional mutations. Thus, MLL-PTD+ cases with additional RUNX1 mutations or FLT3-internal tandem duplication relapsed significantly faster than cases without one of those two mutations (Wilcoxon rank sum test, P = 0·042). As rapid relapses occurred in all MLL subgroups, frequent sampling are necessary to obtain acceptable relapse detection rates and times from molecular relapse to haematological relapse (blood sampling every second month: MLL-PTD: 75%/50 d; MLL translocations: 85%/25 d). In conclusion, in this cohort relapse kinetics is heavily dependent on AML subtype as well as additional genetic aberrations, with possibly great consequences for the rational choice of pre-emptive therapies.
authors.affiliation: Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans B
authors.initials: HB
authors.lastname: Ommen
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Lotte
authors.initials: L
authors.lastname: Abildgaard
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
mesh_terms: D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D020440:Gene Duplication; D052138:Genes, Neoplasm / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D018365:Neoplasm, Residual / Q000235:genetics; D011379:Prognosis; D012008:Recurrence; D020080:Tandem Repeat Sequences / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
keywords: MLL; acute myeloid leukaemia; minimal residual disease; relapse kinetics