This gene encodes a C2H2-type zinc finger protein and is closely related to BCL11A, a gene whose translocation may be associated with B-cell malignancies. The specific function of this gene has not yet been determined, but it could also be involved in some malignancies. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported.[7]
Research suggests that BCL11B is crucial for ameloblasts (the cells that produce tooth enamel) to form and work properly.[10]
BCL11B is closely connected with immune regulation and for so its mutation can lead to a SCID phenotype. This so-called Immunodeficiency 49 (OMIM #617237) is classified as T-B+NK+ SCID.[12] It is characterised by a lack of T lymphocytes and its malfunctioning specifically in proliferative response. On the other hand, B cells and NK cells counts and functions are not impaired.[13] The symptoms of SCID caused by BCL11B mutation - apart from immunity defects - typically include teeth abnormalities, craniofacial dimorphism, different types of dermatitis. As well the intellectual development is significantly impaired. The disease has a very early onset and the only known treatment is hematopoietic stem cell transplantation from a healthy donor.[14][13] The immunodeficiency has a dominant negative mode of inheritance as all so far described patients with it has been after sequencing identified as heterozygotes in the BCL11B gene.[13][14]
Research projects
A mouse model based study showed, that Bcl11b also plays an important role in pathogenesis of inflammatory bowel disease. Bcl11b gene knock-out in certain T cell population led to development of IBD. The mechanisms behind are supposed to be reduced suppressor activity of T regulatory cells and changes in cytokine environment. Bcl11b is suspected to interact with Foxp3 and IL10gene promoters and thus impair its suppressive function in the intestines.[15]
^ abWakabayashi Y, Inoue J, Takahashi Y, Matsuki A, Kosugi-Okano H, Shinbo T, et al. (February 2003). "Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas". Biochemical and Biophysical Research Communications. 301 (2): 598–603. doi:10.1016/S0006-291X(02)03069-3. PMID12565905.
Wakabayashi Y, Inoue J, Takahashi Y, Matsuki A, Kosugi-Okano H, Shinbo T, et al. (February 2003). "Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas". Biochemical and Biophysical Research Communications. 301 (2): 598–603. doi:10.1016/S0006-291X(02)03069-3. PMID12565905.
Bezrookove V, van Zelderen-Bhola SL, Brink A, Szuhai K, Raap AK, Barge R, et al. (February 2004). "A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene". Cancer Genetics and Cytogenetics. 149 (1): 72–6. doi:10.1016/S0165-4608(03)00302-9. PMID15104287.
MacLeod RA, Nagel S, Drexler HG (August 2004). "BCL11B rearrangements probably target T-cell neoplasia rather than acute myelocytic leukemia". Cancer Genetics and Cytogenetics. 153 (1): 88–9. doi:10.1016/j.cancergencyto.2004.02.020. PMID15325104.
Przybylski GK, Dik WA, Wanzeck J, Grabarczyk P, Majunke S, Martin-Subero JI, et al. (February 2005). "Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL". Leukemia. 19 (2): 201–8. doi:10.1038/sj.leu.2403619. PMID15668700. S2CID27146016.
Cismasiu VB, Adamo K, Gecewicz J, Duque J, Lin Q, Avram D (October 2005). "BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter". Oncogene. 24 (45): 6753–64. doi:10.1038/sj.onc.1208904. PMID16091750. S2CID14198939.
Kamimura K, Mishima Y, Obata M, Endo T, Aoyagi Y, Kominami R (August 2007). "Lack of Bcl11b tumor suppressor results in vulnerability to DNA replication stress and damages". Oncogene. 26 (40): 5840–50. doi:10.1038/sj.onc.1210388. PMID17369851. S2CID29677572.
