Cytogenetic analysis

• Provides important prognostic information in both childhood and adult ALL. Abnormalities are detected in up to 85%. The major abnormalities are clonal translocations: t(9;22), t(4;11), t(8;14), t(1;19) or t(10;14) and other structural abnormalities (9p, 6q or 12p). If no structural abnormalities are present, the abnormalities can be classified by the modal chromosome number: <46 (hypodiploid); 46 with other structural abnormalities (pseudodiploid); 47-50 (hyperdiploid); >50 (hyper-hyperdiploid). With the exception of t(9;22) each has an incidence in the order of 5-10% or less.

• t(9;22)(q34;q11) produces the Philadelphia chromosome found in 5% of children and 25% of adults with ALL and is a very strong adverse prognostic factor in both; the resultant BCR-ABL hybrid product is the same 210 kDa protein detected in CML in 33% but is a smaller 180 kDa protein in 66%; it can be used for minimal residual disease detection.

• t(8;14) is associated with B-cell ALL (L3 morphology) and occurs in 5% of cases (dysregulates the myc proto-oncogene), t(1;19) is associated with B-cell precursor ALL; t(4;11) occurs in 80% of infants with ALL and 6% of adults and fuses the MLL gene from 11q23 to the AF4 gene from 4q21 which can be detected by PCR; all these abnormalities are associated with refractory disease and early relapse

• Hyper-hyperdiploidy (>50 chromosomes) confers a favourable prognosis; combined +4, +10 confers a favourable outcome in B-cell precursor ALL; patients with hypoploidy (<46 chromosomes) and pseudodiploidy fare less well.

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