Bcl-2 family members in childhood acute lymphoblastic leukemia: relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome

We have found that, in addition to Bcl-2 and Bar, the expression levels of apoptosis inducers (Bad, Bak) and inhibitors (Bcl-x(L), Mcl-1) were highly variable in blasts from 78 children with newly diagnosed acute lymphoblasti c leukemia (ALL). The patients were enrolled in the national study ALL-7 of the Dutch Childhood Leukemia Study Group. In contrast to Bcl-2 that invers ely correlated with %S-phase cells and WBC, and was lower in T than in B-li neage ALL, the Bcl-2 family members were not found to be associated with fe atures at presentation. These expression levels were also compared with dru g resistance in in vitro MIT (methyl-thiazol-tetrazolium) assays for predni solone, vincristine and asparaginase in 46 children. Protein expression lev els of the Bcl-2 family were not found to correlate with in vitro resistanc e to the individual drugs or the combined drug resistance profile. In addit ion, neither peripheral blast reduction after 1 week of prednisone monother apy nor long-term disease-free interval or survival showed a correlation wi th protein expression. Our results indicate that the anti-proliferative fun ction of BcL-2 dominates its anti-apoptotic function in ALL, but neither Bc l-2 nor the Bcl-2 family members gained prognostic information in the risk- adapted protocol ALL-7.