Pathophysiology

• ~80% childhood ALLs arise in developing B lymphocytes; ~20% in developing T cells. Acquired genetic mutations found in the various sub-types are growing in number as the molecular biology of leukaemia unravels.

• In early B cells commonest mutation is a fusion between the TEL gene at 12p13 and the AML1 gene at 21q22—arises in 20% overall; other common mutations are t(1;19)(q23;p13.3)—8% overall, t(9;22)(q34;q11.2) BCR-ABL (Philadelphia chromosome); 5% overall.

• ~30% have 'high hyperdiploidy' (>50 chromosomes per cell) with or without translocations; 7% show hypodiploidy.

• Infants (<18 months) frequently have a mutation of the MLL gene on chromosome 11 involving a range of fusion partners; most commonly AF4 on chromosome 4.

• The above changes mark biologically different types of precursor B-derived ALL in terms of clinical features and response to treatment.

• 1-2% of ALLs have features of mature B cells and a mutation where the MYC gene is translocated adjacent to the Ig heavy chain locus— t(8;14). Also called Burkitt-type as the cell biology is similar to that of Burkitt's lymphoma.

• T-ALL shows greater genetic diversity than B-derived disease but 12 recurring cytogenetic abnormalities now defined and under study. Clinical importance yet to be defined.

• ALL also classified by immunophenotyping using antibody cell markers for various differentiation antigens designated clusters of differentiation (CD), numbered according to their order of discovery. Immunophenotypes so defined include early pre-B (60%), pre-B (20%), transitional pre-B (1%), B-ALL (1%) and T-ALL (18%).

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