ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis

Jakobczyk, Hélène; Jiang, Yan; Debaize, Lydie; Soubise, Benoît; Avner, Stéphane; Sérandour, Aurélien A.; Rouger-Gaudichon, Jérémie; Rio, Anne-Gaëlle; Carroll, Jason S.; Raslová, Hana; Gilot, David; Liu, Ziling; Demengeot, Jocelyne; Salbert, Gilles; Douet‐Guilbert, Nathalie; Corcos, Laurent; Galibert, Marie‐Dominique; Gandemer, Virginie; Troadec, Marie‐Bérengère

doi:10.1038/s41375-021-01409-9

Cited by 13 publications

(12 citation statements)

References 15 publications

(19 reference statements)

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“…Loss of RUNX1 function has been shown to impair differentiation between myeloid and lymphoid lines and can result in the development of leukaemia. [9][10][11]17,18 The haematological diseases associated with RUNX1 gene include Platelet Disorder diseases, Myeloid Malignancies and Acute Myeloid Leukaemia. 16 RUNX members modulate the transcription of their target genes via recognize the core consensus binding sequence 5′-TGTGGT-3′.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies about RUNX1 gene function have concentrated mainly on the field of haematology. Loss of RUNX1 function has been shown to impair differentiation between myeloid and lymphoid lines and can result in the development of leukaemia 9–11,17,18 . The haematological diseases associated with RUNX1 gene include Platelet Disorder diseases, Myeloid Malignancies and Acute Myeloid Leukaemia 16 .…”

Section: Discussionmentioning

confidence: 99%

“…8 In view of this, previous studies have suggested that RUNX1 may play an important role in regulating organ fibrosis -presumably via interacting with the intracellular TGF-β/Smad signalling pathway. [9][10][11] It has been reported that RUNX1 can regulate renal fibrosis progression via TGF-β signalling. However, the correlation between RUNX1 and liver fibrosis progression remained unclear and required further study.…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported to be a key regulator in the TGF‐β signalling pathway, preventing progression of hepatocellular carcinoma 8 . In view of this, previous studies have suggested that RUNX1 may play an important role in regulating organ fibrosis ‐ presumably via interacting with the intracellular TGF‐β/Smad signalling pathway 9–11 . It has been reported that RUNX1 can regulate renal fibrosis progression via TGF‐β signalling.…”

Section: Introductionmentioning

confidence: 99%

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RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

Guo

Liu

Zhao

et al. 2023

Int J Experimental Path

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Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density‐gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual‐luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl4‐induced conditions. Moreover, α‐SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF‐β/Smads in a dual‐luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF‐β/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

Guo

Liu

Zhao

et al. 2023

Int J Experimental Path

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“…It encodes a transcriptional repressor that plays a critical role in hematopoiesis and maintains HSCs. It is believed that the rearrangement of ETV6 and frequent loss of ETV6 expression could be genetic events that induce leukemia ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel IL3-ETV6 Fusion in Chronic Eosinophilic Leukemia Not Otherwise Specified With t(5; 12) (q31; p13): A Case Report and Literature Review

et al. 2022

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Chronic eosinophilic leukemia not otherwise specified (CEL-NOS) is classified as Myeloproliterative Neoplasms (MPN) and refers to chronic eosinophilic leukemia with some atypical recurrent genetic evidence(1). A rare fusion of ACSL6-ETV6 was previously identified in patients with the t(5;12) (q31; p13) karyotype(2). Here, we report a case of CEL-NOS with a translocation of t(5;12) (q31; p13) and identify IL3-ETV6 transcription, which has not been identified in hematologic diseases. In this patient, eosinophilia was observed. And compared with CEL-NOS patients without ETV6 fusion, a higher mRNA expression level of IL3 was found. After failing treatment with dasatinib, the patient was given hydroxyurea (HU). Subsequently his white blood cell (WBC) and eosinophils decreased significantly and remained in the normal range until publication. Due to the side effects, treatment with HU was replaced by PEG-interferon (PEG-IFN). What’s more, we summarized the case in our study and 21 patients with the karyotype of t(5; 12) (q31; p13) reported by other groups. It was found that most of them had similar clinical manifestations of eosinophilia and tyrosine kinase inhibitor (TKI) insensitivity. The ectopic mRNA expression of IL3 may be the main cause of eosinophilia, and HU and prednisone acetate (PAT), as well as IFN, were considered treatments for this group.

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Childhood Acute Lymphoblastic Leukemia

Rashed,

El-Hadad

2024

Comprehensive Hematology and Stem Cell Research

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ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis

Cited by 13 publications

References 15 publications

RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

A Novel IL3-ETV6 Fusion in Chronic Eosinophilic Leukemia Not Otherwise Specified With t(5; 12) (q31; p13): A Case Report and Literature Review

Childhood Acute Lymphoblastic Leukemia

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