The detection and significance of chromosomal abnormalities in childhood acute lymphoblastic leukaemia

In childhood acute lymphoblastic leukaemia (ALL), cytogenetics plays an ess ential role in diagnosis and prediction of outcome. Conventional cytogeneti c analysis, complemented by fluorescence in situ hybridization (FISH), is h ighly effective in the accurate detection of chromosomal abnormalities. For the precise identification of specific genetic changes, molecular techniqu es may be applied. Chromosomal changes in ALL may be of structural or numer ical type. A large number of established structural chromosomal rearrangeme nts have now been described for which the genetic alterations and effect on prognosis are well known. These include t(9;22)(q34;q11) and BCR/ABL, rear rangements of 1[q23 involving MLL, t(12;21)(p13;q22) with the ETV6/AML1 fus ion,t(l;l 9)(q23;p13) with EZA/PBX1, t(8;14)(q24;q32) and the immunoglobuli n genes. Genetic changes associated with T ALL are also known, although the ir effect on outcome is less pronounced. Rare chromosomal abnormalities are continually being discovered in small patient subgroups leading to the ide ntification of new ALL associated genetic changes. Alterations in chromosom e number have a strong impact on outcome in childhood ALL. The association of a high hyperdiploid karyotype (51-65 chromosomes) with a good prognosis has been known for more than 20 years. Conversely, the loss of chromosomes in the near-haploid group (23-28 chromosomes) indicates a poor outcome. New methods of cancer classification involving gene expression profiling may e ventually supercede cytogenetic analysis in the diagnosis and prediction of outcome in leukaemia. It is more likely that they will be used in a comple mentary approach alongside cytogenetic, FISH and molecular analysis to guid e patient management in childhood ALL. (C) 2001 Harcourt Publishers Ltd.