Unlike solid tumors, the primary strategy for leukemia treatment is chemotherapy. However, leukemia chemotherapy is associated with adverse drug effects and drug resistance. Therefore, it is imperative to identify novel agents that effectively treat leukemia while minimizing adverse effects. The Raf/MEK/extracellular regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3) pathways have been implicated in leukemia carcinogenesis, and provide novel molecular targets for therapeutic intervention in cancer. Mogrol, a biometabolite of mogrosides found in Siraitia grosvenorii, has exhibited anti-cancer activities; however, the underlying mechanism of this effect remains unclear. To clarify its anti-cancer activity and mechanism of action, we treated K562 leukemia cells with mogrol. Mogrol suppressed leukemia cell growth via inhibition of the ERK1/2 and STAT3 pathways, in particular, through the suppression of p-ERK1/2 and p-STAT3. Inhibition of these pathways suppressed Bcl-2 expression, thereby inducing K562 cell apoptosis. Furthermore, mogrol enhanced p21 expression, resulting in G0/G1 cell cycle arrest. The findings provide new perspectives regarding the role of mogrol in leukemia treatment.
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Clin Lymphoma Myeloma Leuk
December 2024
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Hematology Center, Peking University People's Hospital, Qingdao, China. Electronic address:
Aim: To describe tyrosine kinase inhibitor (TKI) treatment patterns and analyze co-variates of TKI switch for chronic myeloid leukemia (CML) patients in a center from China.
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Immunity
January 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, UNSW Sydney, Sydney, NSW, Australia. Electronic address:
The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen.
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January 2025
Leibniz Institute for Immunotherapy (LIT), Division of Genetic Immunotherapy, Regensburg, Germany. Electronic address:
A rapidly growing number of chimeric antigen receptors (CARs) is being translated into cell therapy for malignant and autoimmune diseases. While cancer cell-selective CAR targeting is undergoing continuous refinement, specific testing for overlooked recognition of healthy tissues is commonly not performed, which potentially results in underestimating of the risk of severe tissue damage upon CAR T cell application. Using the FcμR/IgM receptor/FAIM3/TOSO-specific CAR, designed to target chronic lymphocytic leukemia cells, we exemplarily outline a screen to uncover reactivities to healthy tissues and discuss the value of such pre-clinical testing to improve safety in CAR T cell application.
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January 2025
Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:
Background: Stromal cells play a pivotal role in the tumor microenvironment (TME), significantly impacting the progression of acute myeloid leukemia (AML). This study sought to develop a stromal-related prognostic model for AML, aiming to uncover novel prognostic markers and therapeutic targets.
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Biomed Pharmacother
January 2025
Department of Molecular Medicine, Centro de Investigaciones Biológicas Margarita Salas (CIB Margarita Salas-CSIC), Madrid, Spain. Electronic address:
Epigenetic alterations are hallmarks of cancer, with histone modifiers playing critical roles in gene transcription, DNA homeostasis, and other nuclear functions. Lysine-specific demethylase 1 (LSD1), a key regulator of H3K4 methylation, has emerged as a promising pharmacological target in cancer treatment, including leukemia. Acute lymphoblastic leukemia (ALL), the most common pediatric cancer, remains a significant therapeutic challenge due to limited understanding of how epigenetic therapy impacts leukemia dissemination.
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