ALDH and cancer stem cells: Pathways, challenges, and future directions in targeted therapy

Life Sciences, Journal Year: 2024, Volume and Issue: 356, P. 123033 - 123033

Published: Aug. 31, 2024

Language: Английский

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Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8621 - 8621

Published: Aug. 7, 2024

Inflammation is activated by diverse triggers that induce the expression of cytokines and adhesion molecules, which permit a succession molecules cells to deliver stimuli functions help immune system clear primary cause tissue damage, whether this an infection, tumor, or trauma. During inflammation, short-term changes in secretion strong mediators inflammation occur, while long-term occur specific groups cells. Long-term include cellular transdifferentiation for some types need regenerate damaged tissue, as well death can be detrimental integrity if they remain active beyond boundaries essential function. The transcriptional regulator NFκB enables fundamental gene during development. recurrence malignant disease, cell stress-induced alterations enable growth cancer clones are substantially resistant therapeutic intervention system. A number those due significant defects feedback signal cascades control activity NFκB. Specifically, stress contributes it overrides modules otherwise protect host tissue. involved both suppression promotion cancer, key distinctive feature determines its net effect remains unclear. This paper aims provide answer at least one aspect question, namely mechanism divergent response critical inflammatory general.

Language: Английский

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Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(19)

Published: Oct. 1, 2024

Acute myeloid leukaemia (AML) remains a major unmet medical, despite recent progress in targeted molecular therapies. One aspect of leukaemic cell resistance to chemotherapy is the development clones with increased capacity respond cellular stress and production reactive oxygen species (ROS), thanks particular high aldehyde dehydrogenases (ALDH) 1A1/2 activity. At diagnosis, ROS level ALDH1A1/2 activity AML patients BM are correlated different ELN 2022 prognostic groups overall survival (OS). A significant lower was observed favourable ELN2022 subgroup compared intermediate adverse group (p < 0.01). In same way, levels were significantly 0.0001) 0.0002).

Language: Английский

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Proteomic Comparison of Acute Myeloid Leukemia Cells and Normal CD34+ Bone Marrow Cells: Studies of Leukemia Cell Differentiation and Regulation of Iron Metabolism/Ferroptosis

Proteomes, Journal Year: 2025, Volume and Issue: 13(1), P. 11 - 11

Published: Feb. 17, 2025

Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy that can be cured only by intensive chemotherapy possibly combined with allogeneic stem cell transplantation. We compared the pretreatment proteomic profiles of AML cells derived from 50 patients at time first diagnosis normal CD34+ cells. A comparison based on all and populations identified 121 differentially abundant proteins showed least 2-fold differences, these included several markers neutrophil differentiation (e.g., TLR2, integrins ITGM ITGX, downstream mediators including RHO GTPase, S100A8, S100A9, S100A22). However, expression varied between patients, a subset 28 was characterized increased long-term AML-free survival, signs differentiation, favorable genetic abnormalities. These two main patient subsets (28 versus 22 fewer differentiation) also differed regard to phosphorylation 16 proteins. Furthermore, we classified our their involved in regulation iron metabolism/ferroptosis showing differential when comparing Among less prognosis, could then identify genetically heterogeneous adverse prognosis (i.e., death primary resistance/relapse) protein profile similarities conclude differ cells; especially, differences reflecting are associated risk relapse after conventional therapy.

Language: Английский

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ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review)

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(5), P. 1 - 17

Published: March 4, 2025

The expression of cytosolic aldehyde dehydrogenases (ALDHs), which mediate the last step in pathway synthesis all‑trans retinoic acid, is dysregulated various types human cancer, and has been associated with development cancer stem cells (CSCs) solid tumors hematological malignancies. CSCs are considered a minor fraction capacity to initiate neoplastic tumors. ALDH1A1 serves crucial role emergence CSC phenotype, induces malignant behavior promotes treatment resistance. Notably, ALDH1A1‑induced therapy resistance not exclusive just one group drugs, but affects diverse drugs that use different mechanisms kill cells. This diversity drug resistance‑inducing effects stemness‑supporting functions ALDH1A1. inhibition activity using chemicals or depletion via genetic approaches, such as small interfering RNA, can overcome pathways In context breast it critical only expected manifest stem‑like features, include increased From angle disease prognosis, extent association remains be determined through application cutting‑edge methods detect tracked biomarkers within

Language: Английский

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Aldehyde Dehydrogenase Genes as Prospective Actionable Targets in Acute Myeloid Leukemia

Genes, Journal Year: 2023, Volume and Issue: 14(9), P. 1807 - 1807

Published: Sept. 16, 2023

It has been previously shown that the aldehyde dehydrogenase (ALDH) family member ALDH1A1 a significant association with acute myeloid leukemia (AML) patient risk group classification and AML cells lacking expression can be readily killed via chemotherapy. In past, however, redundancy between activities of subgroup members ALDH hampered search for conclusive evidence to address role specific genes. Here, we describe bioinformatics evaluation all nineteen genes as prospective actionable targets development methods aimed improve treatment. We implicate in recurrent AML, show from family, ALDH2 have strongest classification. Furthermore, discover sum values RNA genes, ALDH2, stronger survival than either one gene alone does. conclusion, identify treatment high-risk patients. Substances inhibit both enzymatic constitute potentially effective pharmaceutics.

Language: Английский

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Aldehyde Dehydrogenase Genes as Prospective Actionable Targets in Acute Myeloid Leukemia

Published: July 18, 2023

It has been previously shown that aldehyde dehydrogenase (ALDH) family member ALDH1A1 a significant association with acute myeloid leukemia (AML) patient risk group classification, and AML cells lacking expression can be readily killed by chemotherapy. In the past, however, redundancy between activities of subgroup members ALDH hampered conclusive evidence for addressing role specific genes. We here describe bioinformatics evaluation all nineteen genes as prospective actionable targets development methods aimed to improve treatment. implicate in recurrent AML, we show from family, ALDH2 have strongest classification. Furthermore, discover sum values RNA stronger classification survival than either one gene alone. conclusion, identify treatment high patients. Substances inhibit both enzymatic constitute potentially effective pharmaceutics.

Language: Английский

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OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 148 - 148

Published: Dec. 28, 2023

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes first step in DNA base excision repair pathway, is now also recognized a modulator of gene expression. What important for cancer OGG1 acts NFκB-driven Specifically, oxidant stress cell transiently halts enzymatic activity substrate-bound OGG1. The stalled facilitates binding transactivators, such NFκB to their cognate sites, enabling expression cytokines and chemokines, with ensuing recruitment inflammatory cells. Recently, we highlighted chief aspects involvement regulation expression, hold significance lung development. However, has been implicated molecular underpinning acute myeloid leukemia. This review analyzes discusses how these cells adapt through redox-modulated intricate connections, via interaction NFκB, provides malignant alternative pathways transform microenvironment, adjustment, promoting proliferation, metastasis, evading killing by therapeutic agents.

Language: Английский

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OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer

Published: Nov. 23, 2023

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes first step in DNA base excision repair pathway, is now known also a modulator of gene expression. What important for cancer, OGG1 acts NFκB-driven Specifically, oxidant stress cell transiently halts enzymatic activity substrate-bound OGG1. The stalled facilitates binding transactivators, including NFκB, to their cognate sites enable expression cytokines and chemokines, with ensuing recruitment inflammatory cells. Recently, we highlighted chief aspects involvement regulation expression, have significance lung cancer development. However, has been implicated molecular underpinning acute myeloid leukemia. In general, capacity cells adapt oxidative depends on systems such interface bestows mechanism transformation its microenvironment adaptation survival malignant clones.

Language: Английский

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Molecular characterization and expression profile of the ALDH1A1 gene and its functions in yak luteal cells

Theriogenology, Journal Year: 2024, Volume and Issue: 223, P. 98 - 107

Published: April 30, 2024

Language: Английский

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