Suppressed apoptosis of pre-B cells in bone marrow of pre-leukemic p190(bcr/abl) transgenic mice

Mice transgenic for a p190(bcr/abl) construct develop pre-B cell leukemia/l ymphoma, providing a model of Ph+ ALL. To investigate events in tumorigenes is, immunofluorescence labeling, flow cytometry and a short-term culture as say were used to quantitate precursor B cells and their apoptotic rates in bone marrow of p190(bcr/nbl) transgenic mice over a wide age range. Maligna ncies appeared rapidly at 8-12 weeks of age, followed by slower tumor onset . At 8-12 weeks in normal mice, the apoptotic rate fell among pro-B cells b ut increased steeply among pre-B cells, while the total number of B lineage cells declined. In contrast, in p190(bcr/abl) transgenic mice over the sam e time period, while pro-B cells remained normal in apoptotic rate and numb er, apoptosis of pre-B cells was markedly inhibited and the number of B lym phocytes increased. At later ages (14-30 weeks), B cell precursors in contr ol mice remained constant in apoptotic activity and number, while in the fe w surviving transgenic mice B cell populations were expanded. the results r eveal characteristic changes in apoptotic activity among B cell precursors in bone marrow during early life, severely perturbed in preleukemic p190(bc r/abl) transgenic mice by a preferential suppression of pre-B cell apoptosi s. p190(bcr/abl) may thus promote leukemogenesis by permitting aberrant cel ls generated during early B cell development to evade a normal quality chec kpoint and negative selection.