Glycogen Synthase Kinase-3β (GSK-3β) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia

Tovar, Cristian Fabian Layton; Zerón, Hugo Mendieta; Romero, María del Socorro Camarillo; Sanchez, Yanko Valentin Fabila; Romero, Isidoro

doi:10.17219/acem/63752

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…Besides, GSDMD is mainly expressed in pre-B cells with multiplication capacity, represented by high expression of NF-κB, CD19, and BTK. It is well known that activation of NF-κB and the CD19-BTK axis is essential for promoting B cell growth [ 56 , 57 ]. Herein, targeted activation of TMEM173 in leukemic cells may induce GSDMD-dependent pyroptosis and reduce the tumor burden of B-ALL.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia

et al. 2023

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Background As an essential regulator of type I interferon (IFN) response, TMEM173 participates in immune regulation and cell death induction. In recent studies, activation of TMEM173 has been regarded as a promising strategy for cancer immunotherapy. However, transcriptomic features of TMEM173 in B-cell acute lymphoblastic leukemia (B-ALL) remain elusive. Methods Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were applied to determine the mRNA and protein levels of TMEM173 in peripheral blood mononuclear cells (PBMCs). TMEM173 mutation status was assessed by Sanger sequencing. Single-cell RNA sequencing (scRNA-seq) analysis was performed to explore the expression of TMEM173 in different types of bone marrow (BM) cells. Results The mRNA and protein levels of TMEM173 were increased in PBMCs from B-ALL patients. Besides, frameshift mutation was presented in TMEM173 sequences of 2 B-ALL patients. ScRNA-seq analysis identified the specific transcriptome profiles of TMEM173 in the BM of high-risk B-ALL patients. Specifically, expression levels of TMEM173 in granulocytes, progenitor cells, mast cells, and plasmacytoid dendritic cells (pDCs) were higher than that in B cells, T cells, natural killer (NK) cells, and dendritic cells (DCs). Subset analysis further revealed that TMEM173 and pyroptosis effector gasdermin D (GSDMD) restrained in precursor-B (pre-B) cells with proliferative features, which expressed nuclear factor kappa-B (NF-κB), CD19, and Bruton’s tyrosine kinase (BTK) during the progression of B-ALL. In addition, TMEM173 was associated with the functional activation of NK cells and DCs in B-ALL. Conclusions Our findings provide insights into the transcriptomic features of TMEM173 in the BM of high-risk B-ALL patients. Targeted activation of TMEM173 in specific cells might provide new therapeutic strategies for B-ALL patients.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia

et al. 2023

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“…Those cellular processes are intrinsically regulated by signaling pathways, which mainly control transcription factors that triggers leukemogenesis development [ 12 , 24 , 25 , 42 , 43 , 44 , 45 , 46 ]. The most common pathways involved in leukemia pathogenesis are SCF/c-kit receptor, Notch, HOX, Wnt, EPO-induced, CXCL12-CXCR4, JAK-STAT, and PI3K/AKT/mTOR [ 35 , 36 , 47 ] ( Figure 2 ).…”

Section: Leukemogenesis and Associated Cell Processesmentioning

confidence: 99%

“…The entire process mentioned above is caused and perpetuated by common hallmarks of cancer and includes the following molecular mechanism: limited self-renewal potential, deregulating cellular metabolism, blocking differentiation, resisting cell death, genome instability and mutation, epigenetic reprogramming, growth without restriction, metastasis, inducing angiogenesis, cellular quiescence, altered immunologic response, and niche-promoting inflammation (Figure 1) [35][36][37][38][39][40][41]. Those cellular processes are intrinsically regulated by signaling pathways, which mainly control transcription factors that triggers leukemogenesis development [12,24,25,[42][43][44][45][46]. The most common pathways involved in leukemia pathogenesis are SCF/c-kit receptor, Notch, HOX, Wnt, EPO-induced, CXCL12-CXCR4, JAK-STAT, and PI3K/AKT/mTOR [35,36,47] (Figure 2).…”

Section: Leukemogenesis and Associated Cell Processesmentioning

confidence: 99%

“…Many factors affect the prognosis of BCP-ALL, such as age, the white blood cell (WBC) count, clinical features at diagnosis, cytogenetic abnormalities, pharmacodynamic and pharmacogenetic characteristics of normal patient cells, early response to therapy, and the results of the measurements of minimal/measurable residual disease (MRD: the presence of leukemic cells at specific time points in bone marrow or even in peripheral blood circulation) [ 17 , 18 , 19 , 20 , 21 , 22 ]. The prognostic implication of cytogenic abnormalities relates to poorly regulated signaling pathways [ 5 , 23 ], which can affect leukemogenesis and directly influences ALL development [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia

Álvarez-Zúñiga,

Garza-Veloz,

Martínez-Rendón

et al. 2023

Cancers

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Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the dysfunction of the hematopoietic system that leads to arrest at a specific stage of stem cells development, suppressing the average production of cellular hematologic components. BCP-ALL is a neoplasm of the B-cell lineage progenitor. BCP-ALL is caused and perpetuated by several mechanisms that provide the disease with its tumor potential and genetic and cytological characteristics. These pathological features are used for diagnosis and the prognostication of BCP-ALL. However, most of these paraclinical tools can only be obtained by bone marrow aspiration, which, as it is an invasive study, can delay the diagnosis and follow-up of the disease, in addition to the anesthetic risk it entails for pediatric patients. For this reason, it is crucial to find noninvasive and accessible ways to supply information concerning diagnosis, prognosis, and the monitoring of the disease, such as circulating biomarkers. In oncology, a biomarker is any measurable indicator that demonstrates the presence of malignancy, tumoral behavior, prognosis, or responses to treatments. This review summarizes circulating molecules associated with BCP-ALL with potential diagnostic value, classificatory capacity during monitoring specific clinic features of the disease, and/or capacity to identify each BCP-ALL stage regarding its evolution and outcome of the patients with BCP-ALL. In the same way, we provide and classify biomarkers that may be used in further studies focused on clinical approaches or therapeutic target identification for BCP-ALL.

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“…In glioblastoma multiforme, the most common and most lethal brain tumor, GSK3 inhibitors facilitate apoptosis through inhibition of antiapoptotic mechanisms in mitochondria and inhibit the NFκB pathway that is essential for www.bjbms.org cell survival [56,65]. GSK3β also seems to be responsible for NFκB aberrant activity in pediatric acute lymphoblastic leukemia [66] and pancreatic cancer [67] cells. In renal cancer cells, GSK3 inhibitors induce cell cycle arrest, differentiation of the malignant cells, and autophagy [68].…”

Section: Introductionmentioning

confidence: 99%

The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review

Glibo

Šerman

Karin-Kujundžić

et al. 2020

Bosn J of Basic Med Sci

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Glycogen synthase kinase 3 (GSK3) is a monomeric serine-threonine kinase discovered in 1980 in a rat skeletal muscle. It has been involved in various cellular processes including embryogenesis, immune response, inflammation, apoptosis, autophagy, wound healing, neurodegeneration and carcinogenesis. GSK3 exists in two different isoforms, GSK3α and GSK3β, both containing seven antiparallel beta-plates, a short linking part and an alpha helix, but coded by different genes and variously expressed in human tissues. In the current review, we comprehensively appraise the current literature on the role of GSK3 in various cancers with emphasis on ovarian carcinoma. Our findings indicate that the role of GSK3 in ovarian cancer development cannot be decisively determined as the currently available data support both prooncogenic and tumor-suppressive effects. Likewise, the clinical impact of GSK3 expression on ovarian cancer patients and its potential therapeutic implications are also limited. Further studies are needed to fully elucidate the pathophysiological and clinical implications of GSK3 activity in ovarian cancer.

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Glycogen Synthase Kinase-3β (GSK-3β) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia

Cited by 6 publications

References 22 publications

Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia

Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia

Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia

The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review

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