Efficacy and Safety of Homoharringtonine for the Treatment of Acute Myeloid Leukemia: A Meta-analysis

Mi, Ruihua; Jin, Zhao; Chen, Lin; Wei, Xudong; Liu, Jia

doi:10.1016/j.clml.2021.06.002

Cited by 8 publications

(3 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, several retrospective studies from China, including our own, have consistently shown that patients with AE-AML are less likely to be responsive to VEN plus HMA therapy, regardless of ND or R/R patients [ 7 – 9 , 23 – 25 ]. In ND-AE-AML, Dai et al showed that the standard 7 + 3 regimen acquired a statistically higher response than the VEN plus HMA regimen, with a CR/CRi rate of 61.8% versus 37.8% ( P = 0.02) [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia

Yin,

Yao,

Chen

et al. 2024

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Purpose T(8;21)(q22;q22.1)/AML1-ETO positive acute myeloid leukemia (AE-AML) is sensitive to conventional chemotherapy with a favorable prognosis. However, recent small case reports suggest the limited effectiveness of venetoclax (VEN) and hypomethylating agents (HMA) in treating AE-AML. The aim of this retrospective study was to evaluate the effectiveness of VEN plus AZA (VA) in AE-AML and explore whether adding homoharringtonine (HHT) to VA (VAH) could improve the response. Methods Patients who received VEN plus AZA and HHT (VAH) or VEN plus AZA (VA) regimens were included in this retrospective study. The endpoints of this study were to evaluate the rate of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups. Results A total of 32 AE-AML patients who underwent VA or VAH treatments (newly diagnosed with VA, ND-VA, n = 8; relapsed/refractory with VA, R/R-VA, n = 10; relapsed/refractory with VAH, R/R-VAH, n = 14) were included. The CR (complete remission) /CRi (CR with incomplete count recovery) rate of ND-VA, R/R-VA and R/R-VAH were 25%, 10%, and 64.3%, respectively. Measurable residual disease (MRD) negative was observed in 66.7% of R/R-VAH and none of VA-R/R patients. Co-occurring methylation mutations are associated with poor outcomes with VA but exhibit a more favorable response with VAH treatment. Additionally, patients with c-kit mutation presented inferior outcomes with both VEN-based regimens. All regimens were tolerated well by all patients. Conclusion Our data confirmed the poor response of VA in AE-AML, whether used as frontline or salvage therapy. Adding HHT to VA may improve outcomes and enhance the efficacy of VEN in this population.

show abstract

Section: Discussionmentioning

confidence: 99%

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia

Yin,

Yao,

Chen

et al. 2024

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…[ 6 ] Currently, HHT is widely used in leukemia treatment. [ 7 ] It was shown that HHT could block protein synthesis by competing with incoming aminoacyl-tRNAs to bind to the peptidyl-transferase center. [ 8 , 9 ] In acute myeloid leukemia, HHT affects the DNA epigenome through the SP1/TET1/5hmC axis; [ 10 ] it has been reported to inhibit breast cancer cell growth via the miR-18a-3p/AKT/mTOR signaling pathway [ 11 ] and reduce MYC expression by binding directly to the nuclear factor-kappa B (NF-κB) repressing factor.…”

Section: Introductionmentioning

confidence: 99%

Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model

Qiu,

Zhang,

Tang

et al. 2023

Chinese Medical Journal

View full text Add to dashboard Cite

Background: Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model. Methods: Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results: HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days (P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4+ and CD8+ T cells in the spleen (P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes (CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF)-β pathway-related genes and Treg signature genes (CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4+ Foxp3+ cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions: HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

show abstract

“…In addition, Homoharringtonine (HHT) can be a reliable choice for patients with AML, especially for newly diagnosed or patients younger than 60. Additionally, the use of HHT can reduce relapse in elderly intolerant patients ( Mi et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells

et al. 2022

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is one of the malignant hematological cancers with high mortality. Finding a more effective and readily available treatment is of the utmost importance. Here, we aimed to identify the anti-leukemia effect of a natural small molecule compound honokiol on a panel of AML cell lines, including THP-1, U-937, and SKM-1, and explored honokiol’s potential biological pathways and mechanisms. The results showed that honokiol decreased the viability of the targeted AML cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. Subsequent studies verified that HMOX1 was a critical target in honokiol-induced ferroptosis. These results reveal that honokiol is an effective anti-leukemia agent in AML cell lines and may be a potential ferroptosis activator in AML.

show abstract

Efficacy and Safety of Homoharringtonine for the Treatment of Acute Myeloid Leukemia: A Meta-analysis

Cited by 8 publications

References 12 publications

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia

Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model

Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells

Contact Info

Product

Resources

About