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.
Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Rieka
R
Go
Kazuyoshi
K
Takizawa
Satoshi
S
Hirose
Yoshinori
Y
Katsuragi
Yutaka
Y
Aoyagi
Yukio
Y
Mishima
Ryo
R
Kominami
D000483:Alleles; D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D060168:Thymocytes / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
C511143:Bcl11b protein, mouse; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins