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

• Published in: Leukemia research Vol. 22; no. 8; pp. 677 - 685
• Main Authors: Zinzar, Svetlana, Silverman, Lewis R, Richardson, Eric B, Bekesi, George, Holland, James F
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-08-1998; Elsevier Science
• Subjects: 5-Azacytidine; Antineoplastic agents; Azacitidine - pharmacology; Biological and medical sciences; Biphenotypic; Cell Differentiation - drug effects; Chemotherapy; Cytokines; Differentiation; Drug Synergism; Growth Substances - pharmacology; Humans; Immunophenotyping; Leukemia, Myelomonocytic, Acute - immunology; Leukemia, Myelomonocytic, Acute - pathology; Medical sciences; Myeloid-B lymphoid; Pharmacology. Drug treatments; Recombinant Proteins - pharmacology; Verapamil; Verapamil - pharmacology; ITS, insulin–transferrin–sodium selenite; RA, all- trans-retinoic acid; AcP, acid phosphatase; TNF α, tumor necrosis factor alpha; IL-6, interleukin 6; ICAM-1, intracellular adhesion molecule; RAEB, refractory anemia with excess of blasts; Biphenotypic; 5AzaC, 5-azacytidine; AcP+T, AcP+tartrate; IL-1 α, interleukin 1 α; PHA-LCM, phytohemagglutinin-stimulated lymphocyte conditioned medium; G-CSF, granulocyte colony-stimulating factor; IFN α, interferon-alpha; 5-Azacytidine; RAEB-T, refractory anemia with excess of blasts in transformation; Cytokines; TGF β1, transforming growth factor beta-1; AML, acute myeloid leukemia; ALL, acute lymphoid leukemia; IL-4, interleukin 4; AMML acute myelomonocytic leukemia; GM-CSF, granulocyte-monocyte colony-stimulating factor; IL-3, interleukin 3; IMDM, Iscove's modified Dulbecco medium; CCM, cell-conditioned medium; Myeloid-B lymphoid; IL-7, interleukin 7; VP, verapamil; Verapamil; DMSO, dimethyl sulfoxide; Differentiation; Epo, erythropoietin; FCS, fetal calf serum; PMA, phorbol 12-myristate 13-acetate; Antineoplastic agent; Immunohistochemistry; Cell culture; Flow cytometry; Calcium antagonist; Myelodysplastic syndrome; Myeloproliferative syndrome; Azanucleoside; Azacitidine; Established cell line; Aralkylamine; Phenotypic hybrid; Human; Myelomonocytic leukemia; Acute; Treatment efficiency; Cytokine; Malignant hemopathy; B-Lymphocyte; Cell differentiation; In vitro; Pathology; Antimetabolic; Triazine derivatives; Cytogenetics
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/S0145-2126(98)00020-4

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.