Plasmacytoid blast crisis in B-cell chronic lymphocytic leukemia: effect of estradiol on growth and differentiation in vitro.
Evolution of a case of chronic lymphocytic leukemia (CLL) into blast crisis was found to be characterized by three unusual features (1) the phenotype of the emerging blast cells was that of pre-plasmacytoid cells as shown by plasma cell morphology and an immunological phenotype corresponding partially with CLL- or intermediate B-cells, partially with plasma cells (terminal transferase-, common acute lymphocytic leukemia antigen-, Ia+, surface immunoglobulin heavy chains-, surface kappa light chains+, intracytoplasmic immunoglobulin A+ and G+, BA-1+, polyclonal gammaglobulin production); (2) cytogenetic analysis of spontaneous metaphases revealed that in addition to the typical CLL abnormality, trisomy 12, in all of the cells, an additional translocation between chromosomes 14 and 17 was present in 40% with a presumptive breakpoint on chromosome 14 (q12-3) never described before (commonly q32) and (3) the progression of the disease was associated with a striking increase in the expression by the transformed cells of specific binding sites for estradiol (E2) due to an actual increase in total cellular receptor proteins and not to a change in receptor affinity for E2. The functional status of the steroid receptors was confirmed by nuclear transfer of the cytoplasmic hormone-receptor complex upon temperature activation. Since the rise in E2-receptor display paralleled a large increase in the proliferative activity of the cells as well as a change in their maturation status the question was raised as to whether the E2-receptor should be considered as a physiological marker of growth rate or of cellular differentiation. Exposure of the patient's blast cells to E2 in vitro resulted in cessation of cell growth following at least one mitosis after addition of the inducer as seen from the replacement of the large blasts by small CLL-like cells without definite signs of alteration of the differentiation status. This suggests the association of E2-receptor expression with control of growth rather than cell maturation.
D000368:Aged; D001402:B-Lymphocytes; D002454:Cell Differentiation / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000473:pathology*; D008297:Male; D010950:Plasma Cells / Q000473:pathology; D011959:Receptors, Estradiol / Q000032:analysis
D011959:Receptors, Estradiol; D004958:Estradiol; D004054:Diethylstilbestrol