WT1: a monoclonal antibody reactive with T-ALL but not with other leukemias.

There is ample evidence that the different leukemias represent clonal derivatives of cells "frozen" in a specific state of differentiation or maturation [I]. The hybridoma technology introduced by Köhler and Milstein [2] has permitted the production of monoclonal antibodies directed against differentiation antigens. Such antibodies can contribute considerably to our insight into hemopoietic differentiation and malignancy. Acute lymphoblastic leukemias (ALL) can be subdivided into four subgroups according to membrane markers [3]. In a majority of cases, leukemic cells carry is the common ALL antigen (CALLA), which can be demonstrated with conventional antiserum or with the monoclonal antibody J-5 [4]. The cells from T-ALL patients are reactive with conventional antithymocyte antisera. The rare variant of B-ALL is characterized by the presence of surface immunoglobulin. When the leukemic cells have lymphoid morphology but lack these three markers, the classification "null ALL" has been suggested [3]. The T-ALL subgroup is heterogeneous. Most, but not all, cases are positive for E-rosetting, and sometimes both CALLA and thymocyte antigens are expressed [5, 61. It would be useful if a monoclonal antibody were available which reacts with all T cells and is T-lineage specific. The antibodies from the OKT series are either not T-cell specific (OKT9, OKTIO) or not reactive with the immature T phenotype which is found in the majority of T-ALL cases [7]. Even OKT11 A, reactive with the E-rosette receptor [8], is not ideal since it fails to labe1 those T-ALL which are E-rosette negative. We have produced a monoclonal antibody, termed WT1, which is specific for human thymocytes and T-lymphocytes [9]. This antibody reacts with all thymocytes including the large, terminal deoxynucleotidyl transferase (TdT) positive blasts (Tax, Janossy et al., manuscript in preparation). The reactivity of WTl with this putative prothymocyte population raised the possibility that this antibody might be useful for the diagnosis of T-ALL, especially the immature (E-rosette negative) cases. WTl was therefore tested on a panel of human cell lines of different phenotypes, and on a broad panel of leukemic cells. The results obtained indicate that WT1 is specific for cells of the T lineage and is useful for the diagnosis of T-ALL.