2015 Articles

Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas

Pinkney, Kerice A.; Jiang, Wenxia; Lee, Brian J.; Loredan, Denis G.; Li, Chen; Bhagat, Govind; Zha, Shan

Bcl11b is a transcription factor important for T cell development and also a tumor-suppressor gene that is hemizygously inactivated in ~10 % human T cell acute lymphoblastic leukemia (T-ALL) and several murine T-ALL models, including ATM−/− thymic lymphomas. Here we report that heterozygous loss of Bcl11b (Bcl11b+/−) unexpectedly reduced lethal thymic lymphoma in ATM−/− mice by suppressing lymphoma progression, but not initiation. The suppression was associated with a T cell-mediated immune response in ATM−/−Bcl11b+/− mice, revealing a haploid insufficient function of Bcl11b in immune modulation against lymphoma and offering an explanation for the complex relationship between Bcl11b status with T-ALL prognosis.