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

Christine J. Harrison, Anthony V. Moorman, Kerry E. Barber, Zoë J. Broadfield, Kan L. Cheung, Rachel L. Harris, G. Reza Jalali, Hazel M. Robinson, Jonathan C. Strefford, Adam Stewart, Sarah Wright, Mike Griffiths, Fiona M. Ross, Louise Harewood, Mary 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% (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.

Original languageEnglish (US)
Pages (from-to)520-530
Number of pages11
JournalBritish journal of haematology
Volume129
Issue number4
DOIs
StatePublished - May 1 2005

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Keywords

  • Childhood acute lymphoblastic leukaemia
  • Chromosomal abnormalities
  • Fluorescence in situ hybridization
  • Prognosis

ASJC Scopus subject areas

  • Hematology

Cite this

Harrison, C. J., Moorman, A. V., Barber, K. E., Broadfield, Z. J., Cheung, K. L., Harris, R. L., Jalali, G. R., Robinson, H. M., Strefford, J. C., Stewart, A., Wright, S., Griffiths, M., Ross, F. M., 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, 129(4), 520-530. https://doi.org/10.1111/j.1365-2141.2005.05497.x