Inhibition of BCL11B expression leads to apoptosis of malignant but not normal mature T cells

Grabarczyk, Piotr; Przybylski, Grzegorz K.; Depke, Maren; Völker, Uwe; Bahr, Jeanette; Assmus, K; Bröker, Barbara M.; Walther, Reinhard; Schmidt, Christian A.

doi:10.1038/sj.onc.1210152

Cited by 74 publications

(85 citation statements)

References 35 publications

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“…Our findings are in accordance with the known antiapoptotic role of BCL11B in T-cell malignancies (18)(19)(20). Recently, it has been shown that BCL11B is one of the necessary genes for T-cell differentiation and is associated with T-cell malignancies (21)(22)(23).…”

Section: Discussionsupporting

confidence: 79%

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Gao

et al. 2012

Biomedical Reports

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Abstract. The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11A gene (BCL11A) encodes a krüppel-like zinc finger protein, which is important in thymopoiesis and has been associated with hematopoietic malignancies. In this study, we investigated whether the downregulation of BCL11A mRNA by small interference RNA (siRNA) was capable of inducing apoptosis, and tested the effect of BCL11A siRNA combined with BCL2 siRNA in B lymphoma cell lines (SUDHL6, EB1). BCL11A siRNA was transfected into SUDHL6, EB1 cells with HiPerfect transfection reagents. After transient transfection with BCL11A siRNA, the expression levels of BCL11A mRNA and protein were assayed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis. The cell proliferation was determined by a cell counting kit-8 (CCK8) assay. Apoptosis was determined by morphological observation and flow cytometric analysis. The results showed that the expression levels of BCL11A mRNA and protein from SUDHL6, EB1 cells transfected with BCL11A siRNA decreased, compared with either the scrambled negative control siRNA group or untransfected cells group (P<0.05). Viability of cells transfected with BCL11A siRNA was less compared to cells transfected with control siRNA and untransfected SUDHL6, EB1 cells, respectively (P<0.05). BCL11A siRNA induced apoptosis in both SUDHL6 and EB1 cells. BCL11A siRNA combined with BCL2 siRNA significantly inhibited cell growth. Apoptotic rates of SUDHL6, EB1 cells treated with BCL11A siRNA combined with BCL2 siRNA significantly increased (P<0.05), compared with either the scrambled control (Sc) siRNA and BCL2 siRNA combination or BCL2 or BCL11A siRNA-treated cells alone. Findings of this study suggest the downregulation of BCL11A mRNA by siRNA was able to induce apoptosis.Moreover, BCL11A siRNA combined with BCL2 siRNA increased apoptosis in SUDHL6, EB1 cells. Thus, suppression of BCL11A expression may be a useful approach in the treatment of B lymphoma.

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Section: Discussionsupporting

confidence: 79%

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Gao

et al. 2012

Biomedical Reports

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“…RP11-179F4 (gain: 3 cases; high-level amplification: 2 cases) was found to contain BCL11B, which has been implicated in lymphoid malignancy (13,19,20). Three consecutive BAC clones at 9p21.3 were identified as regions of recurrent homozygous loss (Table 3).…”

Section: Frequencymentioning

confidence: 99%

Array Comparative Genomic Hybridization Analysis of PTCL-U Reveals a Distinct Subgroup with Genetic Alterations Similar to Lymphoma-Type Adult T-Cell Leukemia/Lymphoma

Nakagawa

Nakagawa-Oshiro

Karnan

et al. 2008

Clinical Cancer Research

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Purpose: Peripheral T-cell lymphoma, unspecified (PTCL-U) comprises histopathologically and clinically heterogeneous groups.The purpose of this study was to identify subgroups with distinct genetic, histopathologic, and prognostic features. Experimental Design: We used array comparative genomic hybridization (CGH) for highresolution analysis of 51 PTCL-U patients and the array data for examining possible correlations of histopathologic and clinical features. Moreover, we compared the genetic, histopathologic, and prognostic features of the PTCL-U cases with those of 59 cases of lymphoma-type adult T-cell leukemia/lymphoma (ATLL). Results: We identified 32 regions with frequent genomic imbalance, 1 region with high copy number gain at 14q32.2, and 1 region with homozygous loss at 9p21.3. Gains of 7p and 7q and loss of 9p21.3 showed a significant association with poor prognosis. PTCL-U cases with genomic imbalance showed distinct histopathologic and prognostic features compared with such cases without alteration and a marked genetic, histopathologic, and prognostic resemblance to lymphoma-type ATLL. Conclusions: The array CGH enabled us to identify the frequently altered genomic regions with strong prognostic power among PTCL-U cases. A correlative analysis using the array CGH data disclosed a subgroup in PTCL-U with genomic alterations and with histopathologic and clinical relevance. In addition to histopathologic similarity, the strong genetic and prognostic resemblance between PTCL-U cases with genomic imbalance detected by array CGH and lymphoma-type ATLL seems to support the notion that the former may constitute a distinct PTCL-U subgroup.

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“…On the other hand, Bcl11b +/-heterozygous mice appear normal but are susceptible to thymic lymphomas when they are subjected to gamma radiation [15]. In in vitro studies, selective inhibition of BCL11B in Jurkat cells leads to cell cycle arrest and apoptosis [12,16]. These data suggest that BCL11B is involved in differentiation, cell proliferation and survival in different cell types.…”

Section: Introductionmentioning

confidence: 82%

Bcl11b Heterozygosity Leads to Age-Related Hearing Loss and Degeneration of Outer Hair Cells of the Mouse Cochlea

et al. 2011

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BCL11B/CTIP2 zinc-finger transcription factor is expressed in various types of cells in many different tissues. This study showed that BCL11B is expressed in the nucleus of the outer hair cells of the mouse cochlea, degeneration of which is known to cause deafness and presbycusis or age-related hearing loss (AHL). We tested whether or not Bcl11b heterozygosity would affect AHL in mice. Analysis of auditory brainstem responses revealed AHL in Bcl11b +/-heterozygous, but not wild-type, mice, which was evident as early as 3 months after birth. Histological abnormalities were observed in the outer hair cells of the Bcl11b +/-mice at 6 months of age with hearing loss. These results suggest that the AHL observed in Bcl11b +/-mice is the result of impairment of the outer hair cells and that BCL11B activity is required for the maintenance of outer hair cells and normal hearing.

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Inhibition of BCL11B expression leads to apoptosis of malignant but not normal mature T cells

Cited by 74 publications

References 35 publications

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Downregulation of BCL11A by siRNA induces apoptosis in B lymphoma cell lines

Array Comparative Genomic Hybridization Analysis of PTCL-U Reveals a Distinct Subgroup with Genetic Alterations Similar to Lymphoma-Type Adult T-Cell Leukemia/Lymphoma

Bcl11b Heterozygosity Leads to Age-Related Hearing Loss and Degeneration of Outer Hair Cells of the Mouse Cochlea

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