ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
The most common malignancy in childhood, ALL accounts for 80 % of leukemia in the pediatric age group. ALL is less common in adults, in whom it constitutes approximately 15 % of acute leukemia. ALL is caused by the malignant proliferation of lymphoblasts which are the precursor cells of B and T lymphocytes. ALL is a heterogeneous disorder, and various criteria have been used for subclassification, for example, morphological (e.g., French–American–British classification), immunophenotyping (e.g., T cell, B cell, and various precursor B cell subtypes) or cytogenetic criteria (e.g., t(9;22), t(4;11), t(1;19), and t(12;21)). Immunological classification can be refined by the molecular characterization of immunoglobulin heavy and light chain gene arrangements to define further the cell of origin of ALL.
Childhood leukemia is associated with genetic abnormalities in about 3 % and radiation exposure in less than 8 % of cases, so that the vast majority of cases are unexplained, although an infective (e.g., viral) origin has been postulated. Gunz et al. (1975) found that only 2 % of patients with acute leukemia had a first-degree relative with leukemia, and Till et al. (1975) observed that only 1.4 % of children with ALL had a close relative with leukemia or lymphoma. However, there is a significant risk of childhood leukemia in twins, particularly monozygotic. Thus Miller (1971) estimated that acute leukemia in an identical twin under 6 years of age is associated with a 1 in 6 risk that the co-twin will develop leukemia. The risk of leukemia in the unaffected twin is highest in infancy, decreases with age, and appears to be linked to a shared placental circulation. Thus, it is suggested that the leukemia lineage arises in utero in one twin and migrates to the other (Ford et al. 1993).
Familial clustering of adult ALL has been reported infrequently and might reflect shared environmental and/or genetic factors. De Moor et al. (1988) found 5 of 74 adult patients with ALL had a relative with acute leukemia or lymphoma and that this subgroup of patients with familial leukemia had a greater than expected incidence of HLA-Cw3 antigen.
Horwitz et al. (1996) noted evidence of anticipation in familial leukemia, but for ALL this was based on only four pedigrees, each containing two affected individuals. In contrast to childhood ALL, twin-risks are not high in adult acute leukemia. Specific genetic disorders associated with ALL include Down syndrome, chromosome breakage syndromes (ataxia telangiectasia, Bloom syndrome), Li–Fraumeni syndrome, and immune deficiency disorders (severe combined, Bruton agamma-globulinemia, adenosine deaminase deficiency). Germ-line mutations in PAX5 have recently been identified in familial pre-cell B-ALL (Shah et al. 2013).