Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B-cells.

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Abstract
A special class of human acute lymphocytic leukemias, the common non-T/non-B cell type, was used to define a hierarchy of genetic rearrangements that occur during the earliest stages of B cell maturation. Intermediate cells predicted by a hierarchial model in which Ig H chain variable region gene formation precedes that of L chain and in which .kappa. L chain gene formation precedes that of .lambda. were identified. The model emphasizes the flexible nature of Ig gene recombination that frequently produces aberrant or null genes that are phenotypically excluded from expression. Remaining alleles or isotypic genes can then be utilized as spares, undergoing recombination until a valid gene is formed. The excluded allele or isotype is frequently deleted from the genome. In addition to defining a pathway of genetic maturation, this analysis provides a powerful means to further classify cases of non-T/non-B cell acute lymphocytic leukemia, most of which seem to reside at early stages along the B cell pathway of differentiation.