Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study.

CJ Harrison, AV Moorman, KE Barber, ZJ Broadfield, KL Cheung, RL Harris, GR Jalali, HM Robinson, JC Strefford, A Stewart, S Wright, M Griffiths, FM Ross, L Harewood, M Martineau

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Abstract

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.
Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusPublished - May 2005

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    Harrison, CJ., Moorman, AV., Barber, KE., Broadfield, ZJ., Cheung, KL., Harris, RL., Jalali, GR., Robinson, HM., Strefford, JC., Stewart, A., Wright, S., Griffiths, M., Ross, FM., Harewood, L., & Martineau, M. (2005). Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study. British Journal of Haematology. https://doi.org/10.1111/j.1365-2141.2005.05497.x