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Discovery of a potent PROTAC degrader for RNA demethylase FTO as antileukemic therapy.

Acta Pharm Sin B

December 2024

School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.

The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of -methyladenosine (mA); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown.

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Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the mainstay of treatment for adults with high-risk acute lymphoblastic leukemia (ALL). Due to the crucial role of measurable residual disease (MRD) before Allo-HSCT in predicting relapse and the promising anti-leukemia effect of blinatumomab, we documented a short-course, low-dose conditioning regimen incorporating blinatumomab for Allo-HSCT in three ALL patients with positive MRD. Following the administration of the blinatumomab-containing conditioning regimen, all patients attained complete remission (CR) with negative MRD status, and no severe adverse events were observed.

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The Astragalus Membranaceus Herb Attenuates Leukemia by Inhibiting the FLI1 Oncogene and Enhancing Anti-Tumor Immunity.

Int J Mol Sci

December 2024

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 561113, China.

Astragalus membranaceus (AM) herb is a component of traditional Chinese medicine used to treat various cancers. Herein, we demonstrate a strong anti-leukemic effect of AM injected (Ai) into the mouse model of erythroleukemia induced by Friend virus. Chemical analysis combined with mass spectrometry of AM/Ai identified the compounds Betulinic acid, Kaempferol, Hederagenin, and formononetin, all major mediators of leukemia inhibition in culture and in vivo.

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Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking.

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Article Synopsis
  • Moringa oleifera has been traditionally used in Africa and Asia for its medicinal properties and this study explores its potential anti-leukemia effects through its leaf extracts.
  • The research involved treating leukemia cells with different concentrations of aqueous and ethanolic extracts and measuring cell viability, apoptosis, and gene expression.
  • Results indicated that these extracts were more effective on leukemia cells compared to healthy cells, highlighting the potential for Moringa extracts to be developed as a novel treatment for leukemia.
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