Abstract
BackgroundIn a human T-cell acute lymphoblastic leukemia (T-ALL) cell line (Molt-4), siRNA-mediated suppression of BCL11B expression was shown to inhibit proliferation and induce apoptosis, functions which may be related to genes involved in apoptosis (such as TNFSF10 and BCL2L1) and TGF-β pathways (such as SPP1and CREBBP).MethodsThe expression levels of the above mentioned genes and their correlation with the BCL11B gene were analyzed in patients with T-ALL using the TaqMan and SYBR Green I real-time polymerase chain reaction technique.ResultsExpression levels of BCL11B, BCL2L1, and CREBBP mRNA in T-ALL patients were significantly higher than those from healthy controls (P <0.05). In T-ALL patients, the BCL11B expression level was negatively correlated with the BCL2L1 expression level (rs = -0.700; P <0.05), and positively correlated with the SPP1 expression level (rs = 0.683; P <0.05). In healthy controls, the BCL11B expression level did not correlate with the TNFSF10, BCL2L1, SPP1, or CREBBP expression levels.ConclusionsOver-expression of BCL11B might play a role in anti-apoptosis in T-ALL cells through up-regulation of its downstream genes BCL2L1 and CREBBP.
Highlights
In a human T-cell acute lymphoblastic leukemia (T-ALL) cell line (Molt-4), Small interfering RNA (siRNA)-mediated suppression of BCL11B expression was shown to inhibit proliferation and induce apoptosis, functions which may be related to genes involved in apoptosis and TGF-b pathways
The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B (BCL11B) gene plays a crucial role in T-cell development, differentiation, and proliferation [7], and altered expression, mutation, disruption, or rearrangement of BCL11B have been associated with T-cell
Over-expression of BCL11B gene in T-ALL The expression level of BCL11B mRNA in PBMCs from patients with T-ALL (1821.81 ± 1896.58 copies/105 b2 microglobulin (b2M) copies) was significantly higher than that from healthy controls (259.71 ± 182.72 copies/105 b2M copies; t = 2.46; P = 0.039; Figure 1)
Summary
In a human T-cell acute lymphoblastic leukemia (T-ALL) cell line (Molt-4), siRNA-mediated suppression of BCL11B expression was shown to inhibit proliferation and induce apoptosis, functions which may be related to genes involved in apoptosis (such as TNFSF10 and BCL2L1) and TGF-b pathways (such as SPP1and CREBBP). T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of newly diagnosed ALL cases in children and 20-25% of ALL cases in adults [1,2]. The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B (BCL11B) gene plays a crucial role in T-cell development, differentiation, and proliferation [7], and altered expression, mutation, disruption, or rearrangement of BCL11B have been associated with T-cell. BCL-2 family genes and TNFSF10 probably act together through crosstalk between the intrinsic and death receptor-mediated apoptosis pathways [18]. Secreted phosphoprotein 1 (SPP1) is known as OPN and its abnormal activation can stimulate tumor growth, invasion, angiogenesis, and immune suppression, with wideranging effects on cell proliferation, apoptosis, differentiation, and migration [19,20]
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