Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients

Xi, Yang; Dai, Jing; Li, Chenglong; Zheng, Hong; Zhang, Rong; Wang, Xiaodong; Wang, Chunsen; Huang, Xiaobing

doi:10.3389/fmolb.2020.595395

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…leukemia can be managed and controlled by interfering with the regulatory pathways of immune system cytokines and exclusively in the present study the JAK/STAT signaling pathway inhibitors. leukemia signaling through in STAT 1, 3,5 and JAK2 and JAK3 is necessary to increase the ratio of Th1/Th17(T helpers) and decrease T-ALL (32,33), the STAT 1 pathway order to differentiate CD4 + from Th1; it indicates the path of in uence of these cytokines in leukemia and the focal point for disrupting this cycle by inhibitors such as ruxolitinib or ritanserin and prevention of bone marrow (BM) in ammation as well as hematopoietic BM pancytopenia.…”

Section: Discussionmentioning

confidence: 99%

JAK/STAT as therapeutic signaling pathway in leukemia: a systematic review on in vitro inhibitors

Karimi,

Shahvari,

Ghasemi

et al. 2024

Preprint

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Object Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs) is a main signaling pathway in the immune system, autoimmune disease and in many malignancies such as leukemia. Limiting this signaling pathway has so far been investigated in the treatment of some diseases such as lymphoma, and in this systematic review, we will investigate the role of this type in leukemia. Method This systematic review was written based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and the principle of non-bias was respected. All the articles from 2014–2024 were extracted from Web of Science, PubMed and Scopus databases. We extracted the extracting inhibitors, related immunity elements, JAK/STAT kind, side signaling pathway. Results Three authors searched the database, after screening full texts, 17 articles were included. 15 inhibitory drugs for the JAK/STAT pathway were extracted in studies, which inhibit this signaling pathway in vitro and in cultured human leukemic cells. The most signaling pathways in leukemia were limited to STAT 5 and STAT 3, which were inhibited by Thymoquinone, Ritanserin, Dactocilib and Ruxolitinib. On the other hand, leukemic cells act exclusively through the JAK 2 pathway, which was specifically inhibited by Ruxolitinib and AG490. Increased apoptosis of leukemic cells and decreased cell survival was the result of monotherapy and multitherapy of these inhibitors in the studies available to us. Conclusion Inhibition of JAK/STAT pathway is associated with the reduction of leukemic cell growth and apoptosis of these types of cells, which seems to be a great therapeutic potential for clinical studies in all types of leukemia. We suggest that future studies investigate this type of treatment especially in children and evaluate our results.

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Section: Discussionmentioning

confidence: 99%

JAK/STAT as therapeutic signaling pathway in leukemia: a systematic review on in vitro inhibitors

Karimi,

Shahvari,

Ghasemi

et al. 2024

Preprint

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“…Eligible patients were ≥ 18 years old and had relapsed AML or MDS after allo-HSCT, Eastern Cooperative Oncology Group performance status ≤ 3, and expected survival time ≥ 4 months. The exclusion criteria included (1) Patients who were allergic or had contraindications to the drugs; (2) Patients at pregnant or lactation period; (3) Patients with active infection; (4) Patients who smoked or indulged in excessive drinking, affected the outcome of the trial; (5) Patients with mental illness or other conditions could not get informed consent, cooperate with treatment and physical examination; (6) Patients with active bleeding; (7) In the past year, patients had thrombosis, embolism, cerebral hemorrhage, and so on; (8) Patients received surgical treatment, and the operation period was less than 6 weeks; (9) Patients with clinically significant QTC interval prolongation (time of male is more than 450 ms, time of female is more than 470 ms), ventricular tachycardia, atrial fibrillation, and above two degree cardiac block. Patients with myocardial infarction within 1 years, congestive heart failure, coronary artery heart with symptom and needed to be treated.…”

Section: Study Design and Patient Selectionmentioning

confidence: 99%

“…Strikingly, all patients responded. The overall survival (OS) rate was 79.2%, with a relapse-free survival (RFS) rate of 79.2% [ 7 ]. However, the effect of chidamide in patients with frank hematological relapse after HSCT has not been studied.…”

Section: Introductionmentioning

confidence: 99%

A phase II study of chidamide, cytarabine, aclarubicin, granulocyte colony-stimulating factor, and donor lymphocyte infusion for relapsed acute myeloid leukemia and myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

et al. 2023

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Chemotherapy followed by donor lymphocyte infusion (DLI) is a promising treatment for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the best strategy for administering this therapy is still unclear. This study sought to explore the efficacy and safety of chidamide and CAG (cytarabine, aclarubicin, and granulocyte colony-stimulating factor) (CCAG) regimen followed by DLI in relapsed AML/MDS after allo-HSCT. This was a single-arm, phase II trial in patients with relapsed AML/MDS after allo-HSCT. CCAG regimen followed by DLI was given according to the inclusion and exclusion criteria. Twenty adult patients were enrolled. The median follow-up time was 12 months. The complete remission (CR) rate was 45% and the partial remission (PR) rate was 5%. The 1-year overall survival (OS) was 56.7% (95% confidence interval (95% CI), 31.6–75.6%), and the median OS was 19 months. The 1-year relapse-free survival (RFS) was 83.3% (95% CI, 27.3–97.5%). Patients relapsing more than 6 months after HSCT and achieving CR/PR after CCAG plus DLI regimen attained significantly higher survival rates. The cumulative incidence of grade III–IV acute graft-versus-host disease (aGVHD) was 9.4%. There was no treatment-related mortality (TRM). These data suggest that CCAG plus DLI regimen is safe and induces durable remission and superior survival in patients with relapsed AML/MDS after allo-HSCT. Trial registration number: ChiCTR.org identifier: ChiCTR1800017740 and date of registration: August 12, 2018.

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“…During the treatment process, Th1 cells and CD3 + CD4 − CD8 + T cells increased, and Th17 cells decreased, which reflects the effective treatment-related immune effect. Consequently, the elevated ratio of Th1/Th17 could be a potential biomarker for prognosis evaluation (Xi et al, 2021).…”

Section: Hematological Malignanciesmentioning

confidence: 99%

Therapeutic potential of tucidinostat, a subtype-selective HDAC inhibitor, in cancer treatment

Sun

Hong

Ning³

et al. 2022

Front. Pharmacol.

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Histone deacetylase (HDAC) is one of the most characterized epigenetic modifiers, modulating chromatin structure and gene expression, which plays an important role in cell cycle, differentiation and apoptosis. Dysregulation of HDAC promotes cancer progression, thus inhibitors targeting HDACs have evidently shown therapeutic efficacy in multiple cancers. Tucidinostat (formerly known as chidamide), a novel subtype-selective HDAC inhibitor, inhibits Class I HDAC1, HDAC2, HDAC3, as well as Class IIb HDAC10. Tucidinostat is approved in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL), advanced breast cancer and R/R adult T-cell leukemia-lymphoma (ATLL). Compared with other HDAC inhibitors, tucidinostat shows notable antitumor activity, remarkable synergistic effect with immunotherapy, and manageable toxicity. Here, we comprehensively summarize recent advances in tucidinostat as both monotherapy and a regimen of combination therapy in both hematological and solid malignancies in clinic. Further studies will endeavor to identify more combination strategies with tucidinostat and to identify specific clinical biomarkers to predict the therapeutic effect.

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Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients

Cited by 6 publications

References 45 publications

JAK/STAT as therapeutic signaling pathway in leukemia: a systematic review on in vitro inhibitors

JAK/STAT as therapeutic signaling pathway in leukemia: a systematic review on in vitro inhibitors

A phase II study of chidamide, cytarabine, aclarubicin, granulocyte colony-stimulating factor, and donor lymphocyte infusion for relapsed acute myeloid leukemia and myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

Therapeutic potential of tucidinostat, a subtype-selective HDAC inhibitor, in cancer treatment

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