Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study.
Summary Interphase fluorescence in situ hybridization (iFISH) was used independently to reveal chromosomal abnormalities of prognostic importance in a large, consecutive series of children (n = 2367) with acute lymphoblastic leukaemia (ALL). The fusions, TEL/AML1 and BCR/ABL, and rearrangements of the MLL gene occurred at frequencies of 22% (n = 447/2027) (25% in B-lineage ALL), 2% (n = 43/2027) and 2% (n = 47/2016) respectively. There was considerable variation in iFISH signal patterns both between and within patient samples. The TEL/AML1 probe showed the highest incidence of variation (59%, n = 524/884), which included 38 (2%) patients with clustered, multiple copies of AML1. We were thus able to define amplification of AML1 as a new recurrent abnormality in ALL, associated with a poor prognosis. Amplification involving the ABL gene, a rare recurrent abnormality confined to T ALL patients, was identified for the first time. The use of centromeric probes revealed significant hidden high hyperdiploidy of 33% and 59%, respectively, in patients with normal (n = 21/64) or failed (n = 32/54) cytogenetic results. The iFISH contributed significantly to the high success rate of 91% (n = 2114/2323) and the remarkable abnormality detection rate of 89% (n = 1879/2114). This study highlights the importance of iFISH as a complementary tool to cytogenetics in routine screening for significant chromosomal abnormalities in ALL.
Harrison
Christine J
CJ
Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, General Hospital, Southampton SO16 6YD, UK. harrison@soton.ac.uk
Moorman
Anthony V
AV
Barber
Kerry E
KE
Broadfield
Zoë J
ZJ
Cheung
Kan L
KL
Harris
Rachel L
RL
Jalali
G Reza
GR
Robinson
Hazel M
HM
Strefford
Jonathan C
JC
Stewart
Adam
A
Wright
Sarah
S
Griffiths
Mike
M
Ross
Fiona M
FM
Harewood
Louise
L
Martineau
Mary
M
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D050676:Core Binding Factor Alpha 2 Subunit; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D005784:Gene Amplification; D015321:Gene Rearrangement; D016313:Genes, abl; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007399:Interphase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D016044:Fusion Proteins, bcr-abl; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; C497422:KMT2A protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein