BCR/ABL Enhances Growth of Multipotent Progenitor Cells But Does Not Block Their Differentiation Potential In Vitro

Abstract

We have developed an in vitro system for investigating the direct effect of the BCR/ABL oncogene on the growth and differentiation of single multipotent progenitor cells (MPPC). Using this system we demonstrate that MPPC expressing P210 BCR/ABL have an enhanced ability to grow in the presence of very low concentrations of IL-3 or steel locus factor (SLF). MPPC’s expressing P210 BCR/ABL do not exhibit a block in differentiation and can give rise to mast cell, macrophage, granulocyte and B-lymphoid cell lines. Differentiation of the B-lymphoid cell lines can progress to the pre B-cell stage, marked by expression of CD45R (B220) and rearrangements of both heavy chain immunoglobulin gene alleles. Transformation of MPPC’s, initiated by BCR/ABL progresses through defined stages that can be monitored by obvious changes in growth characteristics. These studies demonstrate that BCR/ABL may enhance the growth of MPPC’s without abrogating their differentiation potential. This system should prove useful in evaluating the effect of specific genetic events on leukemogenesis and identifying the molecular signals which regulate normal hematopoietic development.