F.J. Bollum

Antigenic and enzymatic phenotypes of the pre-B subclass of acute lymphoblastic leukaemia.

Abstract Leukaemias of immature B cells (pre-B cells) can be identified by the presence of cytoplasmic IgM in the absence of detectable cell surface immunoglobulin. One hundred and thirty-one cases of acute lymphoblastic leukaemia were assessed for this marker and 29 including both childhood and adult cases were positive. Twenty-eight of these had the phenotype of the major or common (c) ALL subclass, i.e. cALL antigen + , p28,33 antigen + , and were indistinguishable in presenting clinical and haematological features from IgM negative cALL. Variable proportions (10–95%) of leukaemic lymphoblasts contained detectable cytoplasmic IgM indicating differential levels of maturation arrest and a probable close developmental relationship between IgM + cALL and IgM − cALL. Twenty out of 22 of these pre-B ALLs tested had elevated levels of terminal deoxynucleotidyl transferase, double antibody fluorescence tests with anti-TdT and anti-IgM revealing that individual cells contained nuclear TdT and cytoplasmic IgM. In contrast, four cases of the infrequent B-ALL subgroup had the phenotype p28,33 + , cALL − and TdT negative indicating that the latter enzyme is a correlate of immaturity in both the T and B cell lineage. Eight out of 19 cases of pre-B ALL also had elevated levels of the I (intermediate) isoenzyme peak of hexosaminidase in common with the majority of cases of non-T, non-B or common ALL. These observations provide further insight into the possible target cells and levels of maturation arrest in ALL.

Terminal Transferase Positive Cells in the Human Bone Marrow and Thymus

The original impetus for this study has been the urge for a better understanding of human leukaemias, and the need for developing sensitive single cell assays to recognize individual leukaemic cells. In order to achieve this aim, more had to be learned about the normal human cell types (so-called ‘normal equivalent’ cells) from which the leukaemias originate (1). Terminal deoxynucleotidyl transferase (TdT) is one of the most useful markers in this respect for the following reasons. First, TdT is present in the vast majority of acute lymphoblastic leukaemias (ALL, ref.2,3); thus anti-TdT antibody, developed by Bollum (4), can be used as a “pointer” to specifically recognize leukaemic cells (e.g. residual malignant cells in treated patients) and their normal counterparts. Second, being a nuclear enzyme it is convenient to use anti-TdT antibody in combinations with various antisera reacting with membrane antigens. With the help of these combined assays a surprisingly extensive phenotypic profiles can be assembled about the TdT positive cells in the bone marrow (BM)and thymus. These studies represent the overture for studies which will isolate these human cells and further analyse their functional characteristics and development potential in vitro.