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Human Monoclonal Antibodies Reactive with Human Myelomonocytic Leukemia Cells¹

From the Division of Hematology/Oncology, Department of Medicine, Roger Williams General Hospital, The Roger Williams Cancer Center, and the Brown University Medical School, Providence, Rhode Island 02908

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG₁), HL 2.1 (IgG₃), and HL 3.1 (IgG₁) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000–54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.

¹ This work was supported by a grant (RO1-CA38687) from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Division of Oncology/Hematology, Roger Williams General Hospital, Brown University Medical School, 825 Chalkstone Avenue, Providence, RI 02908.

Received 6/ 7/88. Revised 11/29/88. Accepted 12/29/88.