Correlation of the transcription factors IRF4 and BACH2 with the abnormal NFATC1 expression in T cells from chronic myeloid leukemia patients

Zhang, Yikai; Zeng, Xiangbo; Zha, Xianfeng; Lai, Jing; Tan, Guangxiao; Chen, Shaohua; Yu, Xibao; Li, Yangqiu; Xu, Ling

doi:10.1080/16078454.2022.2066245

Cited by 4 publications

(4 citation statements)

References 51 publications

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“…Chronic Myeloid Leukemia (CML, ORPHA:521) is associated with BACH2 deficiency. Recently, (Zhang et al 2022 ) reported that the expression of IRF4 and BACH2 is notably down regulated in CML patient T cells. Lymphocyte maturation defects and upper respiratory chest infections have been reported in patients with BACH2 heterozygous mutations (Afzali et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Knockout mouse models as a resource for the study of rare diseases

et al. 2023

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Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestations and low prevalence. There is a lack of specific treatments and only a few hundred of the approximately 7,000 RDs have an approved regime. Rapid technological development in genome sequencing enables the mass identification of potential candidates that in their mutated form could trigger diseases but are often not confirmed to be causal. Knockout (KO) mouse models are essential to understand the causality of genes by allowing highly standardized research into the pathogenesis of diseases. The German Mouse Clinic (GMC) is one of the pioneers in mouse research and successfully uses (preclinical) data obtained from single-gene KO mutants for research into monogenic RDs. As part of the International Mouse Phenotyping Consortium (IMPC) and INFRAFRONTIER, the pan-European consortium for modeling human diseases, the GMC expands these preclinical data toward global collaborative approaches with researchers, clinicians, and patient groups.Here, we highlight proprietary genes that when deleted mimic clinical phenotypes associated with known RD targets (Nacc1, Bach2, Klotho alpha). We focus on recognized RD genes with no pre-existing KO mouse models (Kansl1l, Acsf3, Pcdhgb2, Rabgap1, Cox7a2) which highlight novel phenotypes capable of optimizing clinical diagnosis. In addition, we present genes with intriguing phenotypic data (Zdhhc5, Wsb2) that are not presently associated with known human RDs.This report provides comprehensive evidence for genes that when deleted cause differences in the KO mouse across multiple organs, providing a huge translational potential for further understanding monogenic RDs and their clinical spectrum. Genetic KO studies in mice are valuable to further explore the underlying physiological mechanisms and their overall therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Knockout mouse models as a resource for the study of rare diseases

et al. 2023

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“…A proinflammatory microenvironment is thought to sustain tumor progression and disease severity in the context of MPNs [21]; recently, IRF4 downregulation was associated with a worse prognosis in Ph-MPNs [3]. Notably, low IRF4 expression in the context of CML has been associated with perturbation of the transcriptional network of CD3+ T lymphocytes, leading to dysfunctional immune surveillance [22]. Based on these observations, we aimed to evaluate the IRF4 role in the context of CML.…”

Section: Discussionmentioning

confidence: 99%

IRF4 Gene Expression on the Trail of Molecular Response: Looking at Chronic Myeloid Leukemia from Another Perspective

et al. 2022

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Introduction Interferon regulatory factor 4 (IRF4) is a transcriptional factor with a key role in the modulation of inflammation and immune surveillance. The IRF4 gene is downregulated in Philadelphia-negative myeloproliferative neoplasms, and its expression is associated with prognosis and response to treatment. Methods We evaluated the IRF4 expression kinetics during tyrosine kinase inhibitor (TKI) treatment in a cohort of 116 chronic myeloid leukemia (CML) patients to elucidate its role in the disease course. Results A relationship between the IRF4 expression and the disease burden was observed at various disease stages. A correlation analysis between the International Scale (IS) and IRF4 values confirmed this close association. A significant increase is detected after 3 months of TKI treatment. Patients achieving early molecular response (EMR) had higher IRF4 values at both diagnosis and after 3 months of therapy as compared to those failing the EMR target. Patients achieving treatment-free remission (TFR) did not show IRF4 fluctuations during monitoring, while a decreased IRF4 expression emerged at the time of molecular relapse. Conclusion Our data seem to confirm the relevance of IRF4 in the pathogenesis of CML, suggesting a pivotal role at the disease onset and a predictive value during the CML course.

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“…Bach2 (BTB And CNC Homology 1, Basic leucine zipper transcription factor 2) Chronic Myeloid Leukemia (CML, ORPHA:521) is associated with BACH2 de ciency. Recently, (Zhang et al 2022) reported that the expression of IRF4 and BACH2 is notably down regulated in CML patient T cells. Lymphocyte maturation defects and upper respiratory chest infections have been reported in patients with BACH2 heterozygous mutations (Afzali et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Knockout mouse models as a resource for rare diseases studies

Silva-Buttkus

Spielmann

Klein-Rodewald

et al. 2022

Preprint

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Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestation and low prevalence. There is a lack of specific treatments and only a few hundred of the approximately 7.000 RDs have an approved regime. Rapid technological development in genome sequencing enables the mass identification of potential candidates that in their mutated form could trigger diseases but are often not confirmed to be causal. Knockout (KO) mouse models are essential to understand the causality of genes by allowing highly standardized research into the pathogenesis of diseases. The German Mouse Clinic (GMC) is one of the pioneers in mouse research and successfully uses (preclinical) data obtained from single-gene KO mutants for research into monogenic RDs. As part of the International Mouse Phenotyping Consortium and INFRAFRONTIER, the pan-European consortium for modelling human diseases, the GMC expands these preclinical data towards global collaborative approaches with researchers, clinicians and patient groups. Here, we highlight proprietary genes like proof-of-concept RD targets (Nacc1, Bach2, Klotho alpha). We focus on recognized RD genes with no pre-existing KO mouse models (Kansl1l, Acsf3, Pcdhgb2, Rabgap1, Cox7a2) and novel phenotypes capable of optimising clinical diagnostic (Rabgap1, Pcdhgb2). In addition, we present yet unknown RD genes with intriguing phenotypic data (Zdhhc5, Wsb2) not presently associated with known human RDs that may have a justified case to suggest causal genes underlying so far undiagnosed diseases. This report provides comprehensive evidence for genes that when deleted cause differences in the KO mouse across multiple organs, providing a huge translational potential for further understanding monogenic RDs and their clinical spectrum. Genetic KO studies in mice are valuable to explore further the underlying physiological mechanisms and its overall therapeutic potential.

show abstract

Correlation of the transcription factors IRF4 and BACH2 with the abnormal NFATC1 expression in T cells from chronic myeloid leukemia patients

Cited by 4 publications

References 51 publications

Knockout mouse models as a resource for the study of rare diseases

Knockout mouse models as a resource for the study of rare diseases

IRF4 Gene Expression on the Trail of Molecular Response: Looking at Chronic Myeloid Leukemia from Another Perspective

Knockout mouse models as a resource for rare diseases studies

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