Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique
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Updated: Jun 15, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Brian V Balgobind1, Iris H I M Hollink, Dirk Reinhardt
1Paediatric Oncology/Haematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
Abstract:
Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies in paediatric AML are scarce, and reported large differences in the frequency of MLL-PTD, frequently utilising mRNA RT-PCR only to detect MLL-PTDs. We studied the frequency of MLL-PTD in a large cohort of paediatric AML (n=276) and the results from two different methods, i.e. mRNA RT-PCR, and multiplex ligation-dependent probe amplification (MLPA), a method designed to detect copy number differences of specific DNA sequences. In some patients with an MLL-rearrangement, MLL-PTD transcripts were detected, but were not confirmed by DNA-MLPA, indicating that DNA-MLPA can more accurately detect MLL-PTD compared to mRNA RT-PCR. In paediatric AML, MLL-PTD was detected in 7/276 patients (2.5%). One case had a trisomy 11, while the others had normal cytogenetics. Furthermore 4 of the 7 patients revealed a FLT3-ITD, which was significantly higher compared with the other AML cases (p=0.016). In conclusion, using DNA-MLPA as a novel screenings technique in combination with mRNA RT-PCR a low frequency of MLL-PTD in paediatric AML was found. Larger prospective studies are needed to further define the prognostic relevance of MLL-PTD in paediatric AML.
Insights
Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) occur in 2.5% of pediatric acute myeloid leukaemia (AML) cases. DNA-MLPA is a more accurate method for detecting MLL-PTDs than mRNA RT-PCR.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are known genetic alterations in adult acute myeloid leukaemia (AML).
- MLL-PTDs are associated with poor prognosis in adult AML and often co-occur with trisomy 11 or FLT3-ITD.
- Research on MLL-PTDs in pediatric AML is limited, with inconsistent frequency reports often relying solely on mRNA RT-PCR.
Purpose of the Study:
- To determine the frequency of MLL-PTDs in a large cohort of pediatric AML patients.
- To compare the diagnostic accuracy of multiplex ligation-dependent probe amplification (MLPA) with mRNA RT-PCR for MLL-PTD detection.
- To investigate the clinical relevance of MLL-PTDs in pediatric AML.
Main Methods:
- Analysis of a cohort of 276 pediatric AML patients.
- Utilized both mRNA RT-PCR and DNA-based MLPA to detect MLL-PTDs.
- Statistical analysis to compare MLL-PTD frequency and co-occurrence with other genetic alterations.
Main Results:
- MLL-PTDs were detected in 2.5% (7/276) of pediatric AML cases.
- DNA-MLPA proved more accurate than mRNA RT-PCR in confirming MLL-PTDs.
- One patient had trisomy 11; the rest had normal cytogenetics.
- FLT3-ITD was present in 4 of the 7 patients with MLL-PTDs, a significantly higher rate (p=0.016).
Conclusions:
- DNA-MLPA is a reliable screening technique for MLL-PTDs in pediatric AML.
- MLL-PTDs are infrequent in pediatric AML but may be associated with FLT3-ITD.
- Further large-scale studies are required to establish the prognostic significance of MLL-PTDs in pediatric AML.
