Azacytidine plus verapamil induces the differentiation of a newly characterized biphenotypic human myeloid-B lymphoid leukemic cell line BW-90

The biphenotypic cell line BW-90 was established from the peripheral blood of a a patient with a refractory acute myelomonocytic leukemia. All cells were HLADr⁺, CD34^-. Dual color flow cytometry showed simultaneous expression of myeloid (CD33) and B-lymphoid surface markers (CD19) on 60% of cells, CD54 on 91% of cells. Lymphoid lineage markers included CD20/CD22 coexpressed on 89% of cells, CD71 (70%), CD11a (48%), CD18 (54%), and surface lambda light chain (33%). Exposure to various cytokines individually and in combination for up to 14 days had no effect on cell proliferation or differentiation. Only long-term (10-14 days) exposure to 5637 cell-conditioned medium (CCM) induced growth inhibition and differentiation along the monocytic pathway. Differentiation-inducing agents retinoic acid (RA), dimethyl sulfoxide (DMSO) and phorbol 12-myristate 13-acetate (PMA) did not induce differentiation. Differentiation into the monocytic pathway was induced by 5-azacytidine (5AzaC) alone or in combination with verapamil (VP). The BW-90 cell line may serve as a model to study early steps of leukemogenesis and early hematopoiesis. It may provide insight leading to development of an effective therapy for treatment-resistant biphenotypic leukemias.