Update of ALDH as a Potential Biomarker and Therapeutic Target for AML

Yang, Xiangchou; Yao, Rongxin; Wang, Hong

doi:10.1155/2018/9192104

Cited by 24 publications

(18 citation statements)

References 48 publications

(58 reference statements)

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“…These processes are involved in the prognosis of AML. [25][26][27] Moreover, CD133 expression is highly associated with chemoresistance and prognosis of patients with AML. 28 Our results showed that AKAP9 silencing decreases the expression of ALDH1A1 and CD133 in AML cells.…”

Section: Discussionmentioning

confidence: 99%

AKAP9 Upregulation Predicts Unfavorable Prognosis in Pediatric Acute Myeloid Leukemia and Promotes Stemness Properties via the Wnt/β-Catenin Pathway

Shen

Zhao

2022

CMAR

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Background: PRKA kinase anchor protein 9 (AKAP9) is a scaffold protein involved in various cellular processes, including cell adhesion, proliferation, differentiation, and apoptosis. Although the oncogenic role of AKAP9 in solid tumors is well elucidated, the functions and mechanisms of AKAP9 in acute myeloid leukemia (AML) are still not understood. Methods: We used the gene expression omnibus (GEO) database (GSE2191) to determine the mRNA expression of AKAP9 in the bone marrow of pediatric AML and healthy patients. We further used the therapeutically available research to generate effective treatments (TARGET) database to elucidate the relationship between AKAP9 expression and clinical outcomes in pediatric patients with AML. In addition, cell proliferation, cell cycle, apoptosis, RT-PCR, and Western blotting assays were applied to reveal the functions of AKAP9 and the underlying mechanisms of AKAP9 silencing in THP1 and HL60 cell lines. Results: AKAP9 is overexpressed in the bone marrow of pediatric AML patients as compared with that of healthy patients. High expression of AKAP9 was found to be a predictor of poor overall survival (OS) and event-free survival (EFS). Using univariate and multivariate survival analyses, we found that high AKAP9 expression is an independent predictor of a worse OS and EFS. Functionally, AKAP9 silencing significantly inhibited AML cell proliferation, and cell cycle progression and promoted apoptosis. Moreover, AKAP9 silencing significantly downregulated the expression of stemness markers and βcatenin. Conclusion: AKAP9 upregulation is a predictor of unfavorable prognosis, promotes stemness, and activates the Wnt/β-catenin pathway in AML patients. AKAP9 may act as a prognostic biomarker of AML in pediatric patients and a future therapeutic target.

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Section: Discussionmentioning

confidence: 99%

AKAP9 Upregulation Predicts Unfavorable Prognosis in Pediatric Acute Myeloid Leukemia and Promotes Stemness Properties via the Wnt/β-Catenin Pathway

Shen

Zhao

2022

CMAR

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“…Acute myeloid leukemia (AML) is the most common type of myeloid malignancy in adults, and with the exception of the acute promyelocytic leukemia (APL, M3) subtype, this disease has an overall poor prognosis with limited change in the standard of care [1,2]. In leukemic environments, regulatory T cells (Tregs) contribute to immune escape by suppressing antileukemia activity, and these cells include multiple T cell subsets that control the immune response through a variety of mechanisms [3].…”

Section: Introductionmentioning

confidence: 99%

Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients

Jin

Lan

et al. 2020

BioMed Research International

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Foxp3+ γδ regulatory T (γδ Treg) cells promote tumor growth by various mechanisms and induce immuno-senescence. The novel immune checkpoint coinhibitory receptor T cell Ig and ITIM domain (TIGIT) shares similar ligands as the costimulatory receptor DNAX accessory molecule 1 (DNAM-1) and suppresses T cell responses in tumor patients. This study is aimed at characterizing whether the TIGIT/DNAM-1 axis is involved in the distribution and expression of Foxp3+ γδ Treg cell subsets in acute myeloid leukemia (AML) patients of different clinical statuses: de novo AML (27 patients), AML in nonremission (NR) (7 patients), and AML in complete remission (CR) (12 patients). Our data demonstrated that the proportions of Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+ γδ T cells are significantly higher in de novo and NR patients. High levels of TIGIT and DNAM-1 on Foxp3+ γδ T cells correlated with increased Foxp3+ γδ T cell frequencies. In addition, a high TIGIT/DNAM-1 ratio was observed in de novo AML patients and healthy individuals (HIs). Furthermore, the phenotypic abnormalities in Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+ γδ T cells were restored when the patients achieved CR after chemotherapy. Moreover, higher TIGIT+Foxp3+ γδ T cells were associated with AML patients who had poor overall survival and were an independent risk factor for prognosis. In conclusion, our study reveals for the first time that the TIGIT/DNAM-1 axis may be involved in Foxp3+ γδ Treg cells and indicates the clinical progression and prognosis of AML patients of different clinical statuses, which is considered beneficial for efficient AML immunotherapy.

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“…Importantly, deregulation of RA signaling is one of the hallmarks of carcinogenesis and autoimmune diseases [169,170]. In this context, ALDHs activity may be considered not only as a prognostic marker but also as a potential therapeutic target [171][172][173][174]. In fact, compelling evidence indicates the ALDHs involvement in regulation of cell proliferation, survival, and chemoresistance of cancer stem cells [175,176].…”

Section: Unidirectional Production Of Retinoic Acidmentioning

confidence: 99%

The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates

Widjaja‐Adhi

Golczak

2020

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Update of ALDH as a Potential Biomarker and Therapeutic Target for AML

Cited by 24 publications

References 48 publications

AKAP9 Upregulation Predicts Unfavorable Prognosis in Pediatric Acute Myeloid Leukemia and Promotes Stemness Properties via the Wnt/β-Catenin Pathway

AKAP9 Upregulation Predicts Unfavorable Prognosis in Pediatric Acute Myeloid Leukemia and Promotes Stemness Properties via the Wnt/β-Catenin Pathway

Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients

The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates

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