THE EFFECT OF CYTOKINES, INCLUDING IL4, IL7, STEM-CELL FACTOR, INSULIN-LIKE-GROWTH-FACTOR ON CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

We have investigated the effects of some interleukins, such as interle ukin (IL) 4, IL-7, stem cell factor (SCF) and insulin-like growth fact or (IGF-1), known to be involved in human lymphopoiesis, on proliferat ion, clonal growth and differentiation of cells from two acute lymphob lastic leukemia (ALL) derived pre-B cell lines, that is, Nalm 1, Nalm 6 and purified blasts from 37 childhood ALL. IL4 did not display any p romoting activity, an inhibitory effect being observed in two patients . IL7 showed an heterogeneous responsiveness, not related to immunophe notype or cytogenetic features, proliferation and clonal growth being observed in a minority of ALL. In other patients no or even inhibitory effects on proliferation were observed. In one case this inhibition o f DNA synthesis was accompanied by maturation of the cells, as demonst rated by the induced expression of surface immunoglobulins (slg); othe r IL7 treated samples failed to express slg, but showed a decreased ex pression of terminal deoxynucleotidyl transferase and cALL antigen, su ggesting that the cells have a potential of limited maturation by IL7. SCF, known to synergize with IL7 in the most primitive stages of norm al B cell development, did not enhance the IL7 response in B cell prec ursor ALL. Finally IGF-1 failed to induce a proliferative response and clonal growth in BCP ALL either alone or in combination with IL7. (C) 1997 Elsevier Science Ltd.