Loss of Growth Arrest DNA Damage 45b (GADD45b) Enhances Oncogenicity in BCR/ABL-Induced Chronic Myelogenous Leukemia

Growth arrest DNA damage 45b (GADD45b) is upregulated during myeloid lineage terminal differentiation. It is also involved in G2/M cell cycle arrest and apoptosis in response to exogenous stress stimuli. To investigate the effect of GADD45b in the development of leukemia, lethally irradiated mice were reconstituted with either wildtype or gadd45b null myeloid progenitors which retrovirally expressed 210-kD BCR/ABL fusion oncoprotein. We found that both wildtype and gadd45b null myeloid progenitors expressing BCR/ABL induced chronic myelogenous leukemia (CML)-like disease between 11days to 22days after bone marrow transplantation in recipients. However, gadd45b null recipients had a shorter latency (11days–19days) compared to those of wildtypes (14days–22days). This result implies that GADD45b acts as a supressor of CML. Data will be presented on further analyzing the phenotypes of these mice.