Etiological Mechanisms in Childhood Acute Lymphoblastic Leukemia

Childhood acute lymphoblastic leukemia (ALL) is a biologically diverse malignancy. The major subsets correspond to B or T precursor cells, although some ALL may originate in lympho—myeloid stem cells. Multiple molecular alterations contribute to the pathogenesis of ALT., including some that are subset specific. In those cases (~5%) with a Philadelphia chromosome, the genetic basis of karyotypic alteration and the resultant activated ABL kinase have been determined and offer new strategies for molecular diagnosis and monitoring. Although these changes at the DNA level are likely to be functionally relevant to the underlying mechanisms of leukemogenesis, the etiology of childhood ALL remains an enigma. A hypothesis is proposed that takes into account geographic and time trend variations in incidence rates, unusual properties of lymphocyte precursors, and promoting effects of immune responses in infancy.