GROWTH REQUIREMENTS OF NORMAL AND LEUKEMIC HUMAN B-CELL PROGENITORS

Leukemic lymphoblasts in B-lineage acute lymphoblastic leukemia (ALL) express morphologic, phenotypic and genotypic features which resemble those of B lymphocyte progenitors in normal bone marrow. Normal immature B cells and cells from most cases of B-lineage ALL rapidly die in vitro unless they are supported by bone marrow-derived stromal feeder layers. Techniques suitable for maintaining normal and leukemic immature B cells in culture have been developed. Thus, the stromal cell types and growth factors that generate a milieu suitable for immature B-cell development can now be elucidated. In addition, the similarities and discrepancies in survival requirements of normal and leukemic B cell precursors can be studied. We postulate that leukemic B cell precursors can survive and expand in microenvironments incapable of supporting their normal counterparts, and that the study of the survival requirements of ALL cells will provide indications about the aggressivity of the disease in vivo. In this review, we discuss the culture conditions that support in vitro survival of human immature B cells, some of the factors that influence their expansion, and the putative molecular basis for the prolonged life-span of leukemic lymphoblasts.