History and classification of human leukemia-lymphoma cell lines.

Continuous human leukemia-lymphoma cell lines have become indispensable tools in hematological research since the establishment of the first human lymphoma cell line Raji in 1963. We summarize here historical landmarks in the establishment of unique leukemia-lymphoma-derived cell lines from the various cell lineages; their special importance in hematopoietic research is emphasized. The first cell lines were derived from African Burkitt lymphomas and were found to integrate the Epstein-Barr virus in their genome leading to the discovery and isolation of this virus. However, it was later recognized that not every cell line derived from a patient with leukemia-lymphoma represents a malignant cell line as residual normal B-lymphocytes can also be immortalized by EBV infection. During the following 20-30 years many other types of hematopoietic cell lines, commonly derived from hematopoietic neoplasms, were established. These panels of cell lines now span almost the whole spectrum of hematopoietic cell lineages (except for dendritric cells) and the various distinct stages of differentiation along the respective cell axes. From early on, cell lines became important tools for basic and clinical hematological research, initially mainly in the field of immunology, but later expanding to other areas also. It became apparent that leukemia-lymphoma cell lines are of monoclonal origin, are arrested at a discrete maturational stage during differentiation in each lineage, and show sustained and growth factor-independent or -dependent unlimited proliferation. Categorization of cell lines might best be based on the physiological stages of hematopoietic differentiation in the various cell lineages. For an adequate classification, detailed characterizations of both the cell lines and the primary cells from which the cell lines originated are absolutely mandatory. In summary, the availability of large numbers of continuous leukemia-lymphoma cell lines has greatly facilitated clinical and immunobiological studies of normal and malignant hematopoiesis. Human leukemia-lymphoma cell lines will continue to provide exquisite model systems for many biomedical disciplines.