Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.
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.
Balgobind
Brian V
BV
Paediatric Oncology/Haematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
Hollink
Iris H I M
IH
Reinhardt
Dirk
D
van Wering
Elisabeth R
ER
de Graaf
Siebold S N
SS
Baruchel
Andre
A
Stary
Jan
J
Beverloo
H Berna
HB
de Greef
Georgine E
GE
Pieters
Rob
R
Zwaan
C Michel
CM
van den Heuvel-Eibrink
Marry M
MM
D001483:Base Sequence; D002648:Child; D005260:Female; D020440:Gene Duplication; D015321:Gene Rearrangement; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020080:Tandem Repeat Sequences / Q000235:genetics*
D051788:Myeloid-Lymphoid Leukemia Protein