Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome

Huang, Xin; Chen, Cunte; Zhong, Mengjun; Geng, Suxia; Zhao, Yujie; Li, Minming; Deng, Chenxin; Zeng, Lizhi; Wu, Ping; Lu, Zhihui; Weng, Jianyu; Du, Xin; Li, Yangqiu

doi:10.1186/s40364-021-00302-y

Cited by 9 publications

(16 citation statements)

References 13 publications

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“…BCL11B was identified as an important role in T-cell function [ 34 ], and its lower expression is associated with adverse clinical outcomes for patients with myelodysplastic syndrome [ 36 ]. DUSP2 can control the activity of the transcription activator signal transducer and the activator of transcription 3 in its regulation of TH17 differentiation [ 37 ], and can also act as an immune checkpoint in T-cell antitumor immunity [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Human Transcriptome Array Analysis Identifies CDR2 as a Novel Suppressed Gene for Kawasaki Disease

et al. 2022

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Kawasaki disease (KD) is a febrile childhood vasculitis that involves the coronary arteries. Most previous studies have focused on the genes activated in the acute phase of KD. However, in this study, we focused on suppressed genes in the acute stage of KD and identified novel targets with clinical significance and potential prognostic value for KD patients. We enrolled 18 patients with KD, 18 healthy controls (HC), and 18 febrile controls (FC) for human transcriptome array analysis. Another 19 healthy controls, 20 febrile controls, and 31 patients with KD were recruited for RT-PCR validation of target mRNA expressions. The results of Human Transcriptome Array (HTA) 2.0 showed 461 genes that were significantly higher in KD and then normalized after IVIG, as well as 99 suppressed genes in KD. Furthermore, we identified the four genes in KD with the most downregulation, including BCL11B, DUSP2, DDX24, and CDR2, as well as the upregulation of their expression following IVIG administration. The mRNA expression of CDR2 by qRT-PCR was the most compatible with the pattern of the HTA2.0 results. Furthermore, we found higher DDX24 mRNA expression in KD patients with CAL when compared to those without CAL 3 weeks after IVIG administration. In summary, activated gene expression represented a majority in the immune response of KD. In this study, we identified CDR2 as a novel suppressed gene for Kawasaki disease via human transcriptome array analysis and DDX24 associated with CAL formation, which may contribute to further understanding of CAL pathogenesis in KD.

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Section: Discussionmentioning

confidence: 99%

Human Transcriptome Array Analysis Identifies CDR2 as a Novel Suppressed Gene for Kawasaki Disease

et al. 2022

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“…In this study, eleven CMs were analyzed, and seven were associated with the prognosis of TCM patients. However, different hematological malignancies may have different immune receptor abnormalities, and the combination of two related immune receptors has greater advantages compared with a single molecule in predicting the prognosis of patients [ 5 , 6 , 8 , 11 ]. Interestingly, CD5 had the strongest correlation with CD6, and low expression of CD5 and CD6 was significantly associated with adverse outcomes in TCM patients.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, TCL accounts for approximately 2% of non-Hodgkin's lymphoma and has a poor prognosis compared with B-cell lymphoma [4]. Gene mutations and abnormal expression are often used as prognostic biomarkers for risk strati cation of cancer patients [5][6][7]. Recently, abnormal expressions of costimulatory and inhibitory molecules were also used as prognostic biomarkers for hematological malignancies [8,9].…”

Section: Introductionmentioning

confidence: 99%

Low Expression of CD5 and CD6 Is Associated with Poor Overall Survival for Patients with T-Cell Malignancies

Sui

Tan

et al. 2022

Journal of Oncology

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Background. T-cell malignancies (TCMs), including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma (TCL), are highly aggressive and have a poor prognosis. To further understand prognostic stratifications and to design targeted therapies, this study aims to explore novel, potential biomarkers based on alterations in immune costimulatory molecules (CMs) for TCMs. Methods. Peripheral blood from 25 de novo T-ALL patients in our clinical center and transcriptome data from 131 to 162 patients with peripheral TCL (PTCL) from the GSE19069 and GSE58445 dataset, respectively, were obtained to assess the expression levels of CMs and their prognostic significance. Results. Seven CMs were associated with overall survival (OS). Among these CMs, CD5 and CD6 had the highest pairwise positive correlation (R = 0.69). CD5 and CD6 were significantly down-regulated in TCM patients compared with healthy individuals (HIs), and lower CD5 and CD6 expression was associated with poor OS for both T-ALL and TCL patients, particularly for patients greater than 60 years old. Furthermore, CD5 was positively correlated with CD6 in TCM patients. Compared with patients who were CD5highCD6high, T-ALL and TCL patients who were CD5lowCD6low had poor OS. Importantly, CD5highCD6high was an independent prognostic predictor for OS in T-ALL (HR = 0.39, 95% CI: 0.23–0.65, P < 0.001 ) and TCL (HR = 0.35, 95% CI: 0.19–0.62, P < 0.001 ) patients. Conclusions. Low expression of CD5 and CD6 was associated with poor OS for TCM patients, and this may be a potential immune biomarker panel for prognostic stratification of TCM patients.

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“…TCF1+ tumor-infiltrating lymphocytes (TILs) have been positively correlated with tumor regression, successful response to anti-PD-1 treatment, and longer overall survival (OS) (27,28). Multiple studies have also found that decreased BCL11B expression predicts inferior clinical outcome in adult standard risk T cell acute lymphoblastic leukemia and myelodysplastic syndrome (29,30). However, the effects of TCF1 and BCL11B expression on the prognosis of CLL patients remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Decreased TCF1 and BCL11B expression predicts poor prognosis for patients with chronic lymphocytic leukemia

et al. 2022

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T cell immune dysfunction is a prominent characteristic of chronic lymphocytic leukemia (CLL) and the main cause of failure for immunotherapy and multi-drug resistance. There remains a lack of specific biomarkers for evaluating T cell immune status with outcome for CLL patients. T cell factor 1 (TCF1, encoded by the TCF7 gene) can be used as a critical determinant of successful anti-tumor immunotherapy and a prognostic indicator in some solid tumors; however, the effects of TCF1 in CLL remain unclear. Here, we first analyzed the biological processes and functions of TCF1 and co-expressing genes using the GEO and STRING databases with the online tools Venny, Circos, and Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then the expression and prognostic values of TCF1 and its partner gene B cell leukemia/lymphoma 11B (BCL11B) were explored for 505 CLL patients from 6 datasets and validated with 50 CLL patients from Henan cancer hospital (HNCH). TCF1 was downregulated in CLL patients, particularly in CD8+ T cells, which was significantly correlated with poor time-to-first treatment (TTFT) and overall survival (OS) as well as short restricted mean survival time (RMST). Function and pathway enrichment analysis revealed that TCF1 was positively correlated with BCL11B, which is involved in regulating the activation and differentiation of T cells in CLL patients. Intriguingly, BCL11B was highly consistent with TCF1 in its decreased expression and prediction of poor prognosis. More importantly, the combination of TCF1 and BCL11B could more accurately assess prognosis than either alone. Additionally, decreased TCF1 and BCL11B expression serves as an independent risk factor for rapid disease progression, coinciding with high-risk indicators, including unmutated IGHV, TP53 alteration, and advanced disease. Altogether, this study demonstrates that decreased TCF1 and BCL11B expression is significantly correlated with poor prognosis, which may be due to decreased TCF1+CD8+ T cells, impairing the effector CD8+ T cell differentiation regulated by TCF1/BCL11B.

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Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome

Cited by 9 publications

References 13 publications

Human Transcriptome Array Analysis Identifies CDR2 as a Novel Suppressed Gene for Kawasaki Disease

Human Transcriptome Array Analysis Identifies CDR2 as a Novel Suppressed Gene for Kawasaki Disease

Low Expression of CD5 and CD6 Is Associated with Poor Overall Survival for Patients with T-Cell Malignancies

Decreased TCF1 and BCL11B expression predicts poor prognosis for patients with chronic lymphocytic leukemia

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