Details

Autor(en) / Beteiligte

• Korsmeyer, S. J.
• Hieter, P. A.
• Ravetch, J. V.
• Poplack, D. G.
• Waldmann, T. A.
• Leder, P.

Titel

Developmental Hierarchy of Immunoglobulin Gene Rearrangements in Human Leukemic Pre-B-Cells

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1981-11, Vol.78 (11), p.7096-7100

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1981

Quelle

MEDLINE

Beschreibungen/Notizen

• We have used a special class of human acute lymphocytic leukemias, the common ``non-T/non-B'' -cell type, to define a hierarchy of genetic rearrangements that occur during the earliest stages of B-cell maturation. This has allowed us to identify intermediate cells predicted by a hierarchial model in which immunoglobulin heavy chain variable region gene formation precedes that of light chain and in which κ light chain gene formation precedes that of λ . The model emphasizes the flexible nature of immunoglobulin gene recombination that not infrequently 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. Significantly, 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.