MF Greaves

The selectivity of monoclonal antibody J-5 (anti-gp 100, common ALL antigen) for normal and leukemic hemopoietic cells has been investigated. J-5 gave concordant reactions with rabbit anti-cALL, coredistributed on the cell surface, and precipitated a similar if not identical glycoprotein from leukemic and normal tissue. Normal, immature lymphoid cells reactive with J-5 were detected in bone marrow and in fetal thymus. In marrow they were largely coincident with the TdT+ population. J-5 defines a major subgroup of ALL (common ALL) with a favorable prognosis. Of 853 non-ALL acute leukemias investigated, 80 were J-5 positive. These included 14 cases diagnosed as AML, 51 TdT+ blast crises of CGL, and 15 cases diagnosed as "AUL." Of the 14 J-5+ AML, 13 were subsequently rediagnosed either as cALL (10 cases) or mixed lymphoid-myeloid leukemias (3 cases). One-hundred forty-three cases of mature lymphoid cell leukemia (91 B, 52 T) were investigated with J-5; 3 cases only, of disseminated B lymphoma, were positive, albeit weakly. A higher proportion of follicular lymphomas are, however, J-5 positive when studied in sections of biopsy material. A similar pattern of selective reactivity was observed in a series of leukemia/lymphoma cell lines. These studies emphasize the diagnostic value of monoclonal anti-cALL reagents.

To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese adult T-cell leukemia (ATL) and T-cell lymphosarcoma cell leukemia (TLCL), a similar cancer of Caribbean blacks. Ninety to 100% of these patients possessed HTLV-specific antibody. Forty-seven and 20% of relatives of ATL and TLCL patients, respectively, and 12 and 4% of healthy donors from ATL and TLCL endemic areas were also antibody positive. Visceral organ involvement, hypercalcemia, and skin manifestation, features of ATL and TLCL, were often seen in other antibody-positive patients. Childhood cancers, most cutaneous T-cell and all non-T-cell leukemias and lymphomas, myeloid leukemias, Hodgkin's disease, and solid tumors were not associated with HTLV. Healthy United States donors and European patients with non-malignant diseases were antibody negative. HTLV is thus associated with a subtype of adult T-cell leukemia-lymphoma, clustered in viral endemic areas, with apparent racial and geographic predilection.

The selectivity of a monoclonal anti-T antibody, designated WT1, has been assessed in a series of 906 leukemias and lymphomas. In acute lymphoblastic leukemias, WT1 reacts comprehensively and selectively with thymic acute lymphoblastic leukemia (ALL) cells in untreated or relapsed patients, thus overriding the extensive antigenic diversity of this cancer and the immaturity of the cell type involved. All 80 cases of thymic ALL examined were WT1-positive. In addition, 18 cases of presumptive prethymic ALL were also WT1-positive, but were unreactive with other maturation-linked T-cell markers. The phenotype WT1+ HLA-DR TdT+ appears to be unique to T-ALL and can therefore be used systematically for the differential diagnosis of this poor prognosis subtype of ALL. Virtually all ALL cases can now be placed into one of two major subgroups representing transformed precursors of either the T- or B-cell lineage. WT1 identifies a single polypeptide of approximately 40,000 mol wt and is similar to two previously described monoclonal antibodies.