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 muri ne B cell precursor (BCP) cells in a distinct fashion, depending on th e stage of maturation of the cells. For instance, the productive rearr angement of the immunoglobulin heavy chain gene has been demonstrated to be essential for the response of BCP cells to IL-7 as the single pr oliferation stimulus. IL-7 activates a receptor that consists of the I L-7R protein and the common gamma chain (gamma(c)). BCP acute lymphobl astic leukemia (BCP-ALL) cells variably respond to IL-7. Among 72 case s of BCP-ALL IL-7 activated DNA synthesis in 34. In four cases inhibit ion 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 resp onse. Firstly we show that, in contrast to the murine BCP cells, the I L-7 response of human BCP-ALL cells did not correlate with the status of Ig(H) chain gene rearrangement and expression, nor with the rearran gement of Ig(L) chain genes. Subsequently, it is demonstrated that IL- 7R protein and transcripts as well as y,transcripts are equally presen t in the IL-7 responsive and nonresponsive BCP-ALL samples, indicating that the defective expression of these chains could not be held respo nsible for IL-7 response failures. Finally, we observed that kit ligan d (KL), known to synergize with IL-7 in the most primitive stages of n ormal B celldevelopment, did not enhance the IL-7 responses of BCP-ALL cells.