TY - JOUR
T1 - Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia
T2 - A UK Cancer Cytogenetics Group Study
AU - Harrison, Christine J.
AU - Moorman, Anthony V.
AU - Barber, Kerry E.
AU - Broadfield, Zoë J.
AU - Cheung, Kan L.
AU - Harris, Rachel L.
AU - Jalali, G. Reza
AU - Robinson, Hazel M.
AU - Strefford, Jonathan C.
AU - Stewart, Adam
AU - Wright, Sarah
AU - Griffiths, Mike
AU - Ross, Fiona M.
AU - Harewood, Louise
AU - Martineau, Mary
PY - 2005/5
Y1 - 2005/5
N2 - 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% (M = 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.
AB - 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% (M = 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.
KW - Childhood acute lymphoblastic leukaemia
KW - Chromosomal abnormalities
KW - Fluorescence in situ hybridization
KW - Prognosis
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U2 - 10.1111/j.1365-2141.2005.05497.x
DO - 10.1111/j.1365-2141.2005.05497.x
M3 - Article
C2 - 15877734
AN - SCOPUS:20044370480
SN - 0007-1048
VL - 129
SP - 520
EP - 530
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -