TY - JOUR
T1 - Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique
AU - Balgobind, Brian V.
AU - Hollink, Iris H.I.M.
AU - Reinhardt, Dirk
AU - van Wering, Elisabeth R.
AU - de Graaf, Siebold S.N.
AU - Baruchel, Andre
AU - Stary, Jan
AU - Beverloo, H. Berna
AU - de Greef, Georgine E.
AU - Pieters, Rob
AU - Zwaan, C. Michel
AU - van den Heuvel-Eibrink, Marry M.
N1 - Funding Information:
This project was funded by the NWO ‘Netherlands Organisation for Scientific Research’ (B.V.B.) and by the Kinder-Oncologisch Centrum Rotterdam (KOCR) (B.V.B. and I.H.I.M.H.).
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - MLL-PTD
KW - MLPA
KW - Paediatric AML
UR - http://www.scopus.com/inward/record.url?scp=77953288751&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2010.02.019
DO - 10.1016/j.ejca.2010.02.019
M3 - Article
C2 - 20233657
AN - SCOPUS:77953288751
SN - 0959-8049
VL - 46
SP - 1892
EP - 1899
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 10
ER -