Infection of Multipotent IL-3-dependent Stem Cells With a Retroviral Vector Containing the IL-3 Gene Confers Density­ dependent Growth Autonomy Without Blocking Differentiation *

It is widely accepted that most naturally occurring leukemias are monoclonally derived from multipotent stem cells [5–7, 17], but the genetic changes leading to their transformation are poorly understood. A useful system in which to study the various processes occurring during leukemogenesis is offered by non-leukemic, multipotent stem cell lines (FDCPmix) established from murine long-term marrow cultures [20]. These cells grow continuously in vitro in the presence of 11–3, but they can also be induced to differentiate into mature granulocytes, macrophages, erythrocytes, and occasionally megakaryocytes, eosinophils, and mast cells by serum factors [20] or in association with marrow stromal cells [20] or certain embryonic mesenchymal cell lines [18]. Recent data have shown that hematopoietic growth-factor-dependent progenitor cell lines acquire growth-factor-independent growth and tumorigenicity when they are infected with retroviral vectors containing genes coding for I1–3 or GM-CSF [10, 11]. However, these studies have been restricted to cell lines which are blocked in differentiation and may therefore not reflect the alterations that occur in stem cells during leukemogenesis. To determine the effects of aberrant expression of I1–3 in differentiation-inducible stem cells we infected FDCPmix cells with a selectable retroviral vector carrying the cDNA of I1–3.