Impairment in differentiation and cell cycle of thymocytes by loss of a Bcl11b tumor suppressor allele that contributes to leukemogenesis.

Genetic changes in T-ALL are classified into type A abnormalities leading to arrest at a specific stage of T-cell differentiation and type B abnormalities that target cellular processes including cell cycle regulation. Mutations and deletion of a BCL11B haploinsuffiecient tumor suppressor allele have been found in 10-16% of T-ALL subgroups. Analysis of Bcl11b(KO/+) mice revealed impaired T-cell differentiation at two different stages and attenuation of γ-ray induced cell-cycle arrest at S/G2/M phase in immature CD8 single positive cells. Hence, those phenotypes provided by loss of a Bcl11b allele favor that Bcl11b mutation belongs to type B abnormalities.