acute lymphoblastic leukaemia (ALL)

c-ALL or early pre-B immunophenotype

this type of leukaemia is most common in children (20-30% of childhood ALL), peaking at 3-5 years although it is rare in infants and has a low incidence in adults (5% of adult ALL); excess of females

high hyperdiploidy is associated with a low white cell count, and FAB type L1 or L2

prognosis for children is good with long term survival of 70%-80%; adults do less well although event free survival of 59% at 3 years has been reported; the good prognosis is thought to be related to leukaemic cell sensitivity to a number of anti-leukaemic drugs and the propensity of cells to respond by apoptosis; it is unclear why a proportion of patients fail to achieve long term remission but there is evidence that higher chromosome counts of >56 chromosomes and the presence of trisomies 4 and 10 may be associated with a good prognosis whereas the presence of i(17q) is clearly associated with a poor prognosis

the hyperdiploid karyotype is thought to arise from a from a single step mechanism; maintenance of heterozygosity has been demonstrated suggesting that the hyperdiploidy does not arise from a near haploid precursor

patients with hyperdiploidy of >50 chromosomes have clones of 51-68 chromosomes; although high hyperdiploid clones are rarely identical, they tend to show a pattern of chromosome gain with extra copies of chromosomes 4, 6, 10, 14, 18 and 21; the gains, apart from chromosome 21, more often result in trisomy rather than tetrasomy for the gained chromosomes

high hyperdiploidy can be detected by application of a panel of probes which will detect the characteristic pattern of gain; this technique can be applied to interphase blasts but care must be exercised in interpretation and the non-random translocations such as t(9;22), t(1;19), t(12;21) and t(4;11) should be excluded by application of appropriate probes

translocations and other structural chromosome abnormalities are present in approximately half of high hyperdiploid cases; duplication 1q is the most common additional change; duplication of 1q, deletion of 6q and random structural abnormalities have no known prognostic impact; however, the presence of non-random translocations such as t(9;22), t(4;11), t(1;19) and t(12;21) indicate that the translocation is most likely the primary change and that the hyperdiploidy is probably a secondary event; in such cases the leukaemia should be classified according to the translocation rather than the ploidy group in order to assign the correct prognostic implications