title: Different stages of B cell differentiation in non-T acute lymphoblastic leukemia.
abstract: Immunoglobulin heavy chain gene rearrangement was evaluated in 19 cases of acute lymphoblastic leukemia (ALL) and correlated with the immunological phenotypic expression on primary or phorbol diester (12-O-tetradecanoylphorbol-13-acetate [TPA])-induced cells. One case of common ALL (cALL), one case of T-ALL, and one undifferentiated acute leukemia that responded to anti-myeloid drugs after unsuccessful anti-lymphoid induction therapy, had germ line heavy chain genes. Rearranged immunoglobulin genes were instead found in 15 of the 16 cALL cases studied and in a case of non-T, non-B, non-common ("null") ALL, which suggested the B cell origin of the neoplastic cells. All cases bearing a heavy chain gene rearrangement were HLA-DR positive. However, the unique cALL case with a germ line configuration was also HLA-DR positive, which confirmed that both the cALL antigen and HLA-DR antigen were not per se expression of B cell commitment. On the other hand, a complete search for B cell-related markers (BA-1 and B1 monoclonal antibodies, as well as cytoplasmic immunoglobulins [CyIg]) in the cALL cases showed that at least one B cell marker could be detected either on primary or on TPA-induced cells in all cases in which a gene rearrangement had occurred. Incubation with TPA allowed the detection of one B cell marker in a case in which the primary cells were negative, and increased the expression of B cell markers in all but one of the cALLs tested. The only cALL case that was not rearranged expressed no B cell markers either on primary or on TPA-induced cells. The non-T, non-B, non-common ("null") case that was rearranged also showed no phenotypic evidence of B cell markers on primary and induced cells. These findings indicate that: (a) practically all cases of cALL appear to be of B cell origin as shown by gene rearrangement analysis; (b) DNA studies are relevant for a more precise characterization of individual cases of undifferentiated acute leukemia; (c) a complete survey for B cell markers may establish the B cell origin of the cALL blasts, as long as the analysis on primary cells is complemented by differentiation induction assessment; and (d) most cases of non-T ALL appear to be characterized by the expansion of neoplastic cells "frozen" at different levels along the B cell differentiation pathway, the first detectable marker being heavy chain gene rearrangement, followed by BA-1, B1, and CyIg expression.
mesh_terms: D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D005796:Genes; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D011995:Recombination, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D007143:Immunoglobulin Heavy Chains; D013755:Tetradecanoylphorbol Acetate