PROBES FOR HIDDEN HYPERDIPLOIDY IN ACUTE LYMPHOBLASTIC-LEUKEMIA

The detection of hyperdiploidy (clones with > 46 chromosomes) in the b one marrow of patients with acute lymphoblastic leukaemia (ALL) is imp ortant because of the prognostic impact of this finding. The high hype rdiploid (HeH) subgroup with 51-68 chromosomes is associated with the best outcome, followed by the low hyperdiploid (HeL) subgroup with 47- 50 chromosomes and the triploid/tetraploid (TT) subgroup with > 68 chr omosomes, which do less well. We present a strategy for the use of flu orescence in situ hybridization (FISH) with chromosome-specific probes to detect hyperdiploidy in interphase cells and to assign cases to a ploidy subgroup. By using a model population of 252 cases, it was seen that ten chromosomes (X, 4, 6, 8, 10, 14, 16, 18, 20, and 21) used in particular combinations and applied in a step-wise manner enabled the detection of 94% of hyperdiploid cases and gave an accurate predictio n of ploidy subgroup in 96% of these cases. The detection and classifi cation of each case required the use of four to six probes over two or three steps. Confirmation that this strategy will achieve this level of detection in other hyperdiploid populations was demonstrated by usi ng 250 published karyotypes. This strategy has an application in detec ting missing or hidden hyperdiploid cases among cases with failed or n ormal cytogenetics. (C) 1996 Wiley-Liss, Inc.