OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways

Zhao, Min; Wang, Jiangyun; Qu, Mei; Zhao, Yao; Wang, Haihua; Yu, Ke; Liu, Ying; Lei, Zi‐Ning; Liu, Hong‐Min; Hu, Zhenbo; Wei, Liuya; Chen, Zhe‐Sheng

doi:10.3389/fcell.2021.652972

Cited by 5 publications

(8 citation statements)

References 35 publications

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“…As a classic differentiation-inducing drug, ATRA has transformed APL from being highly fatal to being highly curable, and the ATRA/arsenic combination programme has cured almost all patients with standard risk APL. 29,30 Interestingly, the effect of ATRAinduced differentiation is insufficient for APL eradication, whereas only PML/RARA loss fully extinguish leukaemia-initiating activity. 31 Therefore, ATRA/arsenic combination programme exerts an anti-tumour effect by induced PML/RARA degradation in cells, from which anti-tumour efficacy could be dissociated from the trancriptomic effect.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, differentiation therapy is a novel treatment for AML. As a classic differentiation‐inducing drug, ATRA has transformed APL from being highly fatal to being highly curable, and the ATRA/arsenic combination programme has cured almost all patients with standard risk APL 29,30 . Interestingly, the effect of ATRA‐induced differentiation is insufficient for APL eradication, whereas only PML/RARA loss fully extinguish leukaemia‐initiating activity 31 …”

Section: Discussionmentioning

confidence: 99%

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The role of E2A in ATPR‐induced cell differentiation and cycle arrest in acute myeloid leukaemia cells

Zhang

Wang

et al. 2022

J Cellular Molecular Medi

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Acute myeloid leukaemia (AML) is a malignant haematopoietic system disease 1 rooted in aberrant bone marrow cells, and its clinical manifestations include fever, frequent infection, 2 easy bleeding and bruising. 3 According to the latest data published by CA: A Cancer Journal for clinicians, the incidence of AML has been increasing worldwide in the past 20 years, whereas the 5-year survival rate for adults is only 30%. 4 The mechanisms of AML pathogenesis involve specific chromosome translocations most commonly involving t (15;17) and t (8;21) ect 5,6 and the pathogenesis pathways are associated with the P53 and AMPK signalling pathways. 7 The most commonly used induction treatment regimen for AML is cytarabine combined with anthracycline agents and stem cell transplantation; however, severe toxic effects, high rates of relapse and resistance are limitations to its application for clinical use. 8,9 In the late 1980s, all-trans retinoic acid (ATRA) was used clinically in patients with acute promyelocytic leukaemia (APL), providing the first successful cure case. 10 However, ATRA has limited efficacy in other AML subtypes, and serious side effects such as retinoic acid

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The role of E2A in ATPR‐induced cell differentiation and cycle arrest in acute myeloid leukaemia cells

Zhang

Wang

et al. 2022

J Cellular Molecular Medi

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“…Kasumi-1 was incubated with 0.5 μM of I13 for 48 h, and the cells were collected for RNA extraction and mRNA sequencing analysis. As described in our previous work ( 16 , 17 ), the cDNA library was sequenced by Illumina genome analyzer. Levels of gene expression were estimated using fragments per kilobase of exon per million fragments mapped (FPKM) values.…”

Section: Methodsmentioning

confidence: 99%

The Histone Deacetylase Inhibitor I13 Induces Differentiation of M2, M3 and M5 Subtypes of Acute Myeloid Leukemia Cells and Leukemic Stem-Like Cells

Zhao

et al. 2022

Front. Oncol.

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Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by reduced differentiation of myeloid cells and uncontrolled cell proliferation. AML is prone to drug resistance and has a high recurrence rate during treatment with cytarabine-based chemotherapy. Our study aims to explore the cell differentiation effect of a potent histone deacetylase inhibitor (HDACi), I13, and its possible mechanism on AML cell lines (Kasumi-1, KG-1, MOLM-13 and NB4). It has been shown that I13 can significantly inhibit proliferation and colony formation of these AML cells by inducing cell differentiation coupled with cell-cycle exit at G0/G1. Mechanically, I13 presented the property of HDAC inhibition, as assessed by the acetylation of histone H3, which led to the differentiation of Kasumi-1 cells. In addition, the HDAC inhibition of I13 likely dictated the activation of the antigen processing and presentation pathway, which maybe has the potential to promote immune cells to recognize leukemic cells and respond directly against leukemic cells. These results indicated that I13 could induce differentiation of M3 and M5 subtypes of AML cells, M2 subtype AML cells with t(8;21) translocation and leukemic stem-like cells. Therefore, I13 could be an alternative compound which is able to overcome differentiation blocks in AML.

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“…The chemical structure of JOA and its analog OGP46 ( Zhao et al, 2021 ) is shown in Figure 1A . The molecular weight of JOA is 348.2.…”

Section: Methodsmentioning

confidence: 99%

Jiyuan oridonin A induces differentiation of acute myeloid leukemia cells including leukemic stem-like cells

Gao

et al. 2022

Front. Pharmacol.

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Acute myeloid leukemia (AML) is an aggressive form of hematological neoplasia characterized by failure of myeloid differentiation. AML is a leading cause of death from leukemia. Cytarabine chemotherapy resistance is a major source of refractory/relapsed AML. A major obstacle to the successful treatment of AML results from residual disease maintained by leukemic stem cells (LSCs), which are mostly resistant to conventional chemotherapy. Here, we determined the effect of a natural compound, Jiyuan oridonin A (JOA), on the differentiation blockade in the M2 subtype [particularly t (8;21)] of AML cells, M3 subtype of AML cells (APL cells), and leukemic stem-like cells both in vitro and in vivo. We found that JOA induced cell differentiation and suppressed the colony formation capacity in various AML cell lines (Kasumi-1, KG-1, MUTZ-8, NB4, and HL-60) without eliciting apoptosis. The mechanism of JOA-induced cell differentiation depends on the specificity of cell type. JOA mediated the differentiation of Kasumi-1 cells by activating the hematopoietic cell lineage signaling pathway, while inhibition of c-MYC was involved in the JOA-induced differentiation of NB4 cells. Moreover, JOA was identified to target leukemic stem-like cells by induced cell differentiation in vivo. These findings demonstrated that JOA could inhibit the proliferation of M2 and M3 subtypes of AML cells and leukemic stem-like cells by overcoming the differentiation blockade, which may offer a novel therapeutic strategy for AML to overcome relapse and drug resistance in patients with AML. Our findings highlight the possibility of using compounds like JOA as a promising differentiation-induced agent for the treatment of AML.

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OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways

Cited by 5 publications

References 35 publications

The role of E2A in ATPR‐induced cell differentiation and cycle arrest in acute myeloid leukaemia cells

The role of E2A in ATPR‐induced cell differentiation and cycle arrest in acute myeloid leukaemia cells

The Histone Deacetylase Inhibitor I13 Induces Differentiation of M2, M3 and M5 Subtypes of Acute Myeloid Leukemia Cells and Leukemic Stem-Like Cells

Jiyuan oridonin A induces differentiation of acute myeloid leukemia cells including leukemic stem-like cells

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