A comprehensive review on mushrooms with potent antileukemic activity: current status and prospects

Background: Leukemia comprises a heterogeneous group of hematologic malignancies and remains a leading cause of cancer-related mortality among young individuals. Although its precise etiology is not fully understood, known risk factors include immunosuppression, exposure to ionizing radiation, carcinogenic chemicals, and oncogenic viruses. Conventional treatment strategies, including cytotoxic agents and chemotherapy, are often effective but are frequently associated with severe adverse effects, therapeutic failure, drug resistance, and poor patient compliance, underscoring the urgent need for safer and more effective therapeutic alternatives. Methods: A comprehensive literature search was conducted using SciVerse Scopus ® (Elsevier Properties S.A., USA), Web of Science ® (Thomson Reuters, USA), and PubMed ® (U.S. National Library of Medicine, USA) from inception to December 2024. Relevant studies were identified using keywords such as “mushrooms,” “leukemia,” “antileukemic properties of mushrooms,” and “blood cancer.” Results: Mushrooms, long valued as functional foods and integral components of traditional medicine, have recently attracted growing scientific interest for their potential anticancer properties, particularly against leukemia. This review highlights medicinal mushrooms with pronounced antileukemic activity and summarizes their mechanisms of action in leukemia prevention and treatment. Species such as Ganoderma lucidum , Agaricus blazei , Coriolus versicolor , and Cordyceps militaris have demonstrated significant inhibitory effects on leukemia cell proliferation and progression by modulating key signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), Hedgehog, Wnt/ β -catenin, p53, and Ras. In addition, these mushrooms exert notable immunomodulatory effects via both immune checkpoint–dependent and immune checkpoint–independent mechanisms. Bioactive constituents such as small molecules, polysaccharides, saccharides, and antitumor proteins derived from mushrooms further contribute to their antileukemic potential. Conclusions: Despite encouraging evidence from a total of 109 in vitro and in vivo studies, the clinical translation of mushroom-derived antileukemic agents remains limited due to challenges such as variability in extract composition, insufficient pharmacokinetic data, and a lack of well-designed clinical trials. Future research should focus on the isolation and standardization of active compounds, mechanistic validation using advanced molecular approaches, optimization of bioavailability, and rigorous preclinical and clinical investigations. Addressing these limitations may facilitate the development of mushroom-based therapeutics as complementary or alternative strategies for leukemia management.