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From pumps to networks: ABC transporters in leukemia resistance and microenvironmental adaptation.

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Τίτλος: From pumps to networks: ABC transporters in leukemia resistance and microenvironmental adaptation.
Συγγραφείς: Jyotirmayee; School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India., Kumar V; Department of Zoology, Multanimal Modi College, Modinagar, Ghaziabad, 201201, Uttar Pradesh, India., Verma M; School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India. malkhey@bhu.ac.in.
Πηγή: Medical oncology (Northwood, London, England) [Med Oncol] 2026 Sep 10; Vol. 43 (10). Date of Electronic Publication: 2026 Sep 10.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer Country of Publication: United States NLM ID: 9435512 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-131X (Electronic) Linking ISSN: 13570560 NLM ISO Abbreviation: Med Oncol Subsets: MEDLINE
Imprint Name(s): Publication: 2011- : New York : Springer
Original Publication: Northwood, Middlesex, England : Science and Technology Letters, c1994-
Ιατρικοί όροι (MeSH): Leukemia*/metabolism , Leukemia*/drug therapy , Leukemia*/pathology , Drug Resistance, Neoplasm*/physiology , ATP-Binding Cassette Transporters*/metabolism , ATP-Binding Cassette Transporters*/genetics , Tumor Microenvironment*/physiology, Humans ; Drug Resistance, Multiple ; Animals ; Signal Transduction
Περίληψη: ATP-binding cassette (ABC) transporters have long been recognized as critical mediators of multidrug resistance (MDR) in leukemia; however, emerging evidence reframes them as adaptive regulators within an integrated resistance network rather than static efflux pumps. This review consolidates recent mechanistic, functional, and translational insights into the role of key transporters, ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP), in drug resistance and microenvironmental adaptation. We describe how stress-responsive transcriptional programs (ATF4/JUN), stromal kinase signaling (PKC-NF-κB), and metabolic reprogramming (ABCC1-glutathione axis) dynamically regulate transporter expression and activity. Additionally, hypoxia/HIF-1α stabilization, lipid raft remodeling, and extracellular vesicle-mediated communication reinforce efflux competence and sustain leukemic stem cell persistence within protective bone marrow niches. Collectively, these data highlight a shift from isolated transporter overexpression toward network-driven multidrug resistance, wherein transcriptional, metabolic, and stromal inputs converge to reduce intracellular drug accumulation and promote relapse. The review also evaluates methodological standards for functional transporter assessment, including inhibitor-controlled efflux assays, and outlines therapeutic strategies targeting regulatory networks, such as stress-pathway inhibition, stromal disruption, and metabolic modulation, to attenuate adaptive efflux and enhance chemosensitivity. Understanding ABC transporters as components of a stress-responsive, microenvironment-integrated network provides a conceptual framework for developing transporter-aware, niche-adapted interventions aimed at overcoming leukemia resistance and achieving durable therapeutic remission.
(© 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent to publish: Not applicable. Ethical approval: This review article does not need ethical approval. Generative AI in scientific writing: Authors have not used any AI tool for the writing of the manuscript. Informed consent: Formal consent is not required for this type of study.
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Contributed Indexing: Keywords: ABC transporters; Bone marrow microenvironment; Leukemia; Multidrug resistance; Stress signaling
Substance Nomenclature: 0 (ATP-Binding Cassette Transporters)
Entry Date(s): Date Created: 20260910 Date Completed: 20260910 Latest Revision: 20261015
Update Code: 20261016
DOI: 10.1007/s12032-026-03400-9
PMID: 42720707
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1559-131X
DOI:10.1007/s12032-026-03400-9