HETEROGENEITY OF PROLIFERATIVE RESPONSES OF HUMAN B-CELL PRECURSOR ACUTE LYMPHOBLASTIC-LEUKEMIA (BCP-ALL) CELLS TO INTERLEUKIN-7 (IL-7) - NO CORRELATION WITH IMMUNOGLOBULIN GENE STATUS AND EXPRESSION OF IL-7 RECEPTOR OR IL-2/IL-4/IL-7 RECEPTOR COMMON GAMMA-CHAIN GENES

Interleukin 7 (IL-7) stimulates proliferation of normal human and murine B cell precursor (BCP) cells in a distinct fashion, depending on the stage of maturation of the cells. For instance, the productive rearrangement of the immunoglobulin heavy chain gene has been demonstrated to be essential for the response of BCP cells to IL-7 as the single proliferation stimulus. IL-7 activates a receptor that consists of the IL-7R protein and the common gamma chain (gamma(c)). BCP acute lymphoblastic leukemia (BCP-ALL) cells variably respond to IL-7. Among 72 cases of BCP-ALL IL-7 activated DNA synthesis in 34. In four cases inhibition of DNA synthesis was seen. In the remaining 38 cases IL-7 exerted no effects. We determined whether this heterogeneity in IL-7 response could be correlated with parameters that could influence the IL-7 response. Firstly we show that, in contrast to the murine BCP cells, the IL-7 response of human BCP-ALL cells did not correlate with the status of Ig(H) chain gene rearrangement and expression, nor with the rearrangement of Ig(L) chain genes. Subsequently, it is demonstrated that IL-7R protein and transcripts as well as y,transcripts are equally present in the IL-7 responsive and nonresponsive BCP-ALL samples, indicating that the defective expression of these chains could not be held responsible for IL-7 response failures. Finally, we observed that kit ligand (KL), known to synergize with IL-7 in the most primitive stages of normal B celldevelopment, did not enhance the IL-7 responses of BCP-ALL cells.