Acute myeloid leukemia (AML) is an aggressive hematological malignancy with limited treatment options. Inflammation is often a contributing factor to the development and progression of AML, and related diseases, and can potentiate therapy failure. Previously, we had identified anti-inflammatory roles and anti-AML efficacy for blueberry extracts. The present study extended these observations to determine that the polyphenol quercetin inhibited neutral sphingomyelinase (N-SMase) activity and exerted anti-AML efficacy. Moreover, quercetin was shown to exert combinatorial anti-AML efficacy with nanoliposomal ceramide. Overall, this demonstrated that quercetin could block the pro-inflammatory actions of N-SMase and augment the efficacy of anti-AML therapeutics, including ceramide-based therapeutics.
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http://dx.doi.org/10.31021/ijbs.20181106 | DOI Listing |
Ann Hematol
November 2024
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
Similar to other malignancies, immune dysregulation is a key feature of acute myeloid leukemia (AML), manifesting as suppressed anti-leukemia immune cells, immune evasion by leukemia blasts, and disease progression. Various immunosuppressive factors within the AML microenvironment contribute to the weakening of host immune responses and the efficacy of cellular immunotherapy. To address these challenges, strategies targeting immunosuppressive elements within the AML microenvironment aim to bolster host or adoptive immune effector cells, ultimately enhancing leukemia treatment.
View Article and Find Full Text PDFAdv Mater
October 2024
Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, P. R. China.
Hematological malignancies (HM) like acute myeloid leukemia (AML) are often intractable. Cancer vaccines possibly inducing robust and broad anti-tumor immune responses may be a promising treatment option for HM. Few effective vaccines against blood cancers are, however, developed to date partly owing to insufficient stimulation of dendritic cells (DCs) in the body and lacking appropriate tumor antigens (Ags).
View Article and Find Full Text PDFExp Hematol
October 2024
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; The University of Queensland, Brisbane, Queensland, Australia. Electronic address:
Acute myeloid leukemia (AML) is a genetically heterogeneous disease, in that a multitude of oncogenic drivers and chromosomal abnormalities have been identified and associated with the leukemic transformation of myeloid blasts. However, little is known as to how individual mutations influence the interaction between the immune system and AML cells and the efficacy of the immune system in AML disease control. In this review, we will discuss how AML cells potentially activate the immune system and what evidence there is to support the role of the immune system in controlling this disease.
View Article and Find Full Text PDFHaematologica
June 2024
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.
Recurrent and/or refractory (R/R) pediatric acute myeloid leukemia (AML) remains a recalcitrant disease with poor outcomes. Cell therapy with genetically modified immune effector cells holds the promise to improve outcomes for R/R AML since it relies on cytotoxic mechanisms that are distinct from chemotherapeutic agents. While T cells expressing chimeric antigen receptors (CAR T cells) showed significant anti-AML activity in preclinical models, early phase clinical studies have demonstrated limited activity, irrespective of the targeted AML antigen.
View Article and Find Full Text PDFJCI Insight
April 2024
Department of Microbiology and Immunology.
Allogeneic hematopoietic stem cell transplantation (aHSCT) can cure patients with otherwise fatal leukemias and lymphomas. However, the benefits of aHSCT are limited by graft-versus-host disease (GVHD). Minnelide, a water-soluble analog of triptolide, has demonstrated potent antiinflammatory and antitumor activity in several preclinical models and has proven both safe and efficacious in clinical trials for advanced gastrointestinal malignancies.
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