Molecular diversity of precursor B acute lymphoblastic leukemias identified by the immunoglobulin heavy chain gene organization.

Acute leukemias with morphological, cytochemical, and immunological characteristics correlating to precursor B lymphocyte and with germ line configuration of immunoglobulin heavy (IgH) chain loci were studied for the organization of antigen receptor genes including C mu, Ig light (IgL) chain, T cell receptor (TCR) beta and gamma. Three of the five lymphoblast samples retained the germ line configuration of both Ig JH and C mu region. The other two samples showed deletion of the entire JH region resulting in the rearrangement of the C mu region. None of these five cases had a Ig L chain gene rearrangement. The three cases with germ line IgJH and C mu loci were revealed to belong to stage I (HLA DR+), stage II (HLADR+, CD19+), and stage III (HLADR+, CD19+, CD10+) B precursor ALLs, respectively. The two cases with deletion of IgJH region also belonged to stage II and III B precursor ALL. Thus immunologically classified stage II and III B precursor ALLs include those with germ line IgH region, representing ALLs at a very early stage of B cell development. A subgroup of B precursor ALL with deleted IgJH region, which is abortive at the molecular genetic level, was also identified. Karyotype abnormalities involving chromosomal region 11q23 in the leukemias with germ line IgH region are also discussed.