IL1RL1 is dynamically expressed on Cbfb-MYH11+ leukemia stem cells and promotes cell survival

Wang, Yiqian; Richter, Lisa; Becker, Michelle; Amador-Ortiz, Catalina; Hyde, R. Katherine

doi:10.1038/s41598-018-38408-3

Cited by 15 publications

(17 citation statements)

References 43 publications

(49 reference statements)

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“…Interestingly, we found that there was a statistically signi cant decrease in cells in G0/G1 phase in IL-33-treated cells, as compared to the untreated cells (Fig.4E). These results are consistent with our earlier work showing that IL-33 inhibits apoptosis via activating p38 MAPK and upregulates the percentage of cells in S phase in primary mouse leukemia cells and human AML cell line [16,18]. Together, our data indicate that IL-33 promotes cell survival by stimulating p38 MAPK pathway in AML patient samples.…”

Section: Il-33 Promotes Cell Survival Via P38 Mapk Pathway In Primarysupporting

confidence: 93%

“…Previously, we found that IL1RL1 is highly expressed in leukemia cells expressing CBFB-MYH11 [16,17]. Further, we demonstrated that exogenous IL-33 treatment inhibited apoptosis of primary mouse leukemia cells as well as human AML cell line, HL-60 [18].…”

Section: Introductionmentioning

confidence: 74%

“…IL-33 is a recently identi ed cytokine that belongs to IL-1 cytokine family [12]. Previously, we showed that IL1RL1, the receptor of IL-33, is highly expressed in leukemia cells expressing Cbfb-MYH11, and exogenous treatment with IL-33 promoted the survival of both primary mouse leukemia cells and human AML cell lines in vitro [16,18]. Further investigation revealed that IL-33/IL1RL1 axis can inhibit leukemia cell apoptosis via phosphorylating p38 MAPK [18].…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-33 Promotes Cell Survival via P38 MAPK-mediated Interleukin-6 Gene Expression and Release in Pediatric AML

Wang

et al. 2020

Preprint

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BackgroundAcute myeloid leukemia (AML) is a fatal disease characterized by an accumulation of immature myeloid blasts in the bone marrow (BM). Cytokine provide signals for leukemia cell to better survive in the BM microenvironment. Previously, we identified interleukin-33 (IL-33) as a stimulator of cell survival in human AML cell line and primary mouse leukemia cells. However, the mechanism on how IL-33 regulates AML activity is not well known.MethodsFlow cytometry, ELISA and cytometric bead array (CBA) were used to investigate the expression of IL1RL1 and serum cytokine levels in AML patient samples and cell culture supernatant. The correlation of serum IL-33 and IL-6 levels was calculated by Pearson R test. Annexin V staining was used to examine the apoptosis of AML cells. RT-PCR was used to measure IL-6 expression in leukemia cells.ResultsThe cell surface expression of IL-33-specific receptor, IL1RL1, is elevated in BM cells from AML patients at diagnosis, and the serum level of IL-33 in AML patients is higher than that of healthy donor controls. Moreover, IL-33 levels are positively associated with IL-6 levels in pediatric patients with AML. In vitro, IL-33 treatment increased IL-6 mRNA expression and protein level in BM and peripheral blood (PB) cells from AML patients. IL-33 inhibited cell apoptosis by activating p38 MAPK pathway using human AML cell line as well as AML patient samples. Finally, IL-33 activated IL-6 expression in a manner that required p38 MAPK pathway using clinical AML samples.ConclusionsTaken together, we demonstrate that p38 MAPK pathway is important for IL-33-mediated anti-apoptotic process as well as cytokine expression and release in pediatric patients with AML.

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Section: Il-33 Promotes Cell Survival Via P38 Mapk Pathway In Primarysupporting

confidence: 93%

Section: Introductionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Interleukin-33 Promotes Cell Survival via P38 MAPK-mediated Interleukin-6 Gene Expression and Release in Pediatric AML

Wang

et al. 2020

Preprint

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“…We must also consider that the IL-33/ST2 system in the BM can be stimulated both in hematopoietic cells and in stromal/nonhematopoietic cells. Activation of ST2 on these cells provokes the production of several cytokines (IL-6, GM-CSF, G-CSF, and IL-3) that can activate the STAT5 pathway and can cause resistance to imatinib mesylate [68,82].…”

Section: Il-33 and Hematologic Malignanciesmentioning

confidence: 99%

“…Employing Cbfb-MYH11 knock-in mice, it was reported that ST2 is present on cells with high leukemia stem cell activity. Moreover, ST2 + cells can survive chemotherapy better than ST2 − cells in vivo [82]. Levescot et al made a similar observation for BCR-ABL1 in CML [77].…”

Section: Il-33 and Hematologic Malignanciesmentioning

confidence: 99%

The ST2/Interleukin-33 Axis in Hematologic Malignancies: The IL-33 Paradox

Allegra

Innao

Tartarisco

et al. 2019

IJMS

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Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an “alarmin” able to stimulate several effectors of the immune system, regulating numerous immune responses comprising cancer immune reactions. IL-33 has been demonstrated to influence tumorigenesis. However, as far as this cytokine is concerned, we are faced with what has sometimes been defined as the IL-33 paradox. Several studies have demonstrated a relevant role of IL-33 to numerous malignancies, where it may have pro- and—less frequently—antitumorigenic actions. In the field of hematological malignancies, the role of IL-33 seems even more complex. Although we can affirm the existence of a negative role of IL-33 in Chronic myelogenos leukemia (CML) and in lymphoproliferative diseases and a positive role in pathologies such as Acute myeloid leukemia (AML), the action of IL-33 seems to be multiple and sometimes contradictory within the same pathology. In the future, we will have to learn to govern the negative aspects of activating the IL-33/ST2 axis and exploit the positive ones.

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Clinical implications and genetical insights of SOX6 expression in acute myeloid leukemia

Jiang

Zhang

et al. 2022

J Cancer Res Clin Oncol

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Background: Transcription factor SOX6 belongs to Sry-related high-mobility-group box (SOX) family, has been reported to be downregulated and act as a tumor-suppressor gene in various solid tumors, but in acute myeloid leukemia (AML) is incompletely understood. Methods: The SOX6 expression was analyzed between AML patients and normal controls from public data and our research cohort. Correlations between SOX6 expression and clinical, genetic features together with survival were further analyzed.Results: In both public and our present datasets, we demonstrated that SOX6 expression is notably downregulated in AML patients compared with normal controls. Moreover, the expression level of SOX6 was dynamic, along with the disease status. SOX6 was signi cantly decreased in relapsed/refractory AML compared with complete remission AML. Clinically, SOX6 underexpression was signifcantly correlated with bone marrow blasts, and WBC counts. Furthermore, decreased expression of SOX6 was more common in core binding factor AML (CBF-AML), rarely found in complex karyotype AML (CK-AML), and correlated with FLT3 mutations. By survival analyses, low-expression of SOX6 was associated with shorter overall survival (OS) and event-free survival (EFS) among cytogenetic normal AML (CN-AML) patients. Moreover, both univariate and multivariate analyses showed that low SOX6 expression was an independent unfavorable prognostic biomarker for CN-AML. Conclusions: Our fndings indicated that SOX6 underexpression, as a frequent event in AML, was associated with genetic abnormalities and prognosis in AML. SOX6 might be a valuable biomarker for risk strati cation, predicting prognosis and relapse of AML.

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IL1RL1 is dynamically expressed on Cbfb-MYH11+ leukemia stem cells and promotes cell survival

Cited by 15 publications

References 43 publications

Interleukin-33 Promotes Cell Survival via P38 MAPK-mediated Interleukin-6 Gene Expression and Release in Pediatric AML

Interleukin-33 Promotes Cell Survival via P38 MAPK-mediated Interleukin-6 Gene Expression and Release in Pediatric AML

The ST2/Interleukin-33 Axis in Hematologic Malignancies: The IL-33 Paradox

Clinical implications and genetical insights of SOX6 expression in acute myeloid leukemia

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