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

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-015-0191-8) contains supplementary material, which is available to authorized users.