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Characterization of novel myeloid differentiation antigen associated with acute myelogenous leukemia Askew, David Stephen


A monoclonal antibody has been developed that detects a unique cell surface antigen (NHL-30.5) with a molecular weight of 180,000 expressed on the human acute promyelocytic cell line HL-60. In addition to HL-60 and other AML cell lines, the antibody reacts with a significant proportion of hemopoietic cells from 40/48 patients with acute myeloid leukemia (AML), and on a variety of other hematologic disorders characterized by the presence of immature myeloid blast cells. In contrast it does not react with normal mature hemopoietic cells, including lymphocytes, monocytes, granulocytes, erythrocytes, platelets, and splenocytes. Only one of 15 acute lymphoblastic leukemias has demonstrated reactivity (weakly) and all lymphoid cell lines tested have been uniformly negative. Reactivity with cells from patients in the chronic phase of chronic myeloid leukemia (CML) is also rare (7/26) and the number of NHL-30.5 positive cells is low (<20%). The acute phase of CML is strongly NHL-30.5-positive if the blast crisis is of the myeloid variant but is clearly negative in lymphoid blast crisis. Analysis of normal differentiating bone marrow cells and mature peripheral blood mononuclear cells stained indirectly with the NHL-30.5 monoclonal antibody and FITC-second antibodies did not reveal a distinctly positive population. However, the cells with the highest fluorescence intensities (comprising 5% of the total population) sorted on a fluorescence activated cell sorter were highly enriched in both erythropoietic (CFU-E/BFU-E) and granulopoietic (CFU-C) progenitors. It therefore appears that the NHL-30.5 antigen is not an AML-associated marker but rather a normal myeloid differentiation antigen that is expressed on immature myeloid cells. Consistent with this hypothesis is the observation that a number of AML- derived cell lines that are blocked at an early stage of maturation lose NHL-30.5 expression when they are induced to terminally differentiate. These results support the concept that undifferentiated myeloid progenitors accumulate in AML patients due to a block in their capacity to differentiate into the stages characterized by loss of the NHL-30.5 antigen. The NHL-30.5 monoclonal antibody identifies a previously undescribed progenitor cell antigen and is potentially a useful reagent to differentiate myeloid leukemias from lymphoid leukemias, particularly in the acute phase of CML.

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