Exploitation of monoclonal antibodies: a "who's who" of haemopoietic malignancy.

A library of monoclonal antibodies plus "conventional' markers (e.g. anti-TdT) have been used to explore the detailed phenotypes of leukaemic cells in relation to normal haemopoietic differentiation. This analysis reveals that consistent, composite phenotypes of different subclasses of lymphoid malignancies closely mimic those of corresponding normal cells at equivalent levels of maturation. It is suggested that three major target cell populations are available for lymphoid malignancy: the pluripotential stem cell (e.g. "lymphoid' blast crisis of CGL), lymphoid progenitors or stem cells in the bone marrow (non-T ALL) or thymus (T-ALL, T-NHL) and long lived, mature and immunocompetent T and B cells (T-CLL, PLL, Sézary and B-CLL, lymphoma respectively). The major phenotypes documented in different leukaemias represent the level of "maturation arrest' imposed on the dominant subclone; this is determined by, but not necessarily synonymous with, the "target cell' and associated clonogenic cell population in the leukaemia. No consistent major abnormalities of gene expression are revealed by this investigation and although they may exist (e.g. loss or acquisition of antigens with malignant progression) we suggest that they are irrelevant to the central issue of what alterations are essential and sufficient for the evolution of clonogenic leukaemic cells. We propose instead that subtle changes, which uncouple proliferation and differentiation, are all that is required.