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.
Zinzar
S
S
The Samuel Bronfman Department of Medicine and Derard H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Silverman
L R
LR
Richardson
E B
EB
Bekesi
G
G
Holland
J F
JF
D001374:Azacitidine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D015479:Leukemia, Myelomonocytic, Acute / Q000276:immunology / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D006133:Growth Substances; D011994:Recombinant Proteins; D014700:Verapamil; D001374:Azacitidine