ArticleBlood2022
Critical role of Lama4 for hematopoiesis regeneration and acute myeloid leukemia progression.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Bone marrow stromal cells promote chemoresistance in acute myeloid leukaemia through P2RX7-mediated antioxidant defence.Experimental & molecular medicine · 2026Article
- Critical role of niche S100A8 for acute myeloid leukemia progression and hematopoiesis regeneration.Blood advances · 2025Article
- Article
- From Chemotherapy to Targeted Therapy: Unraveling Resistance in Acute Myeloid Leukemia Through Genetic and Non-Genetic Insights.International journal of molecular sciences · 2025Review
- C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function.Journal of hematology & oncology · 2025Article
- MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway.Experimental hematology & oncology · 2025Article
- Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting.Nature communications · 2024Article
- Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets.Nature communications · 2024Article
- Mesenchymal stem cells (MSCs) from the mouse bone marrow show differential expression of interferon regulatory factors IRF-1 and IRF-2.Molecular biology reports · 2024Article
- Application and research progress of single cell sequencing technology in leukemia.Frontiers in oncology · 2024Review
- Comprehensive Genomic Analysis of Puerarin in Inhibiting Bladder Urothelial Carcinoma Cell Proliferation and Migration.Recent patents on anti-cancer drug discovery · 2024Article
- Fabrication of a three-dimensional bone marrow niche-like acute myeloid Leukemia disease model by an automated and controlled process using a robotic multicellular bioprinting system.Biomaterials research · 2023Article
- Skin mesenchymal niches maintain and protect AML-initiating stem cells.The Journal of experimental medicine · 2023Article
- Article
- Bone Marrow Microenvironment-Induced Chemoprotection inCancers · 2023Article
- The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia.International journal of molecular sciences · 2023Review
- IncreasedCancers · 2023Article
- CD34Frontiers in cell and developmental biology · 2023Article
- Bone marrow stromal cells reduce low-dose cytarabine-induced differentiation of acute myeloid leukemia.Frontiers in pharmacology · 2023Article
- Mesenchymal stem cells: Emerging concepts and recent advances in their roles in organismal homeostasis and therapy.Frontiers in cellular and infection microbiology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impairment of normal hematopoiesis and leukemia progression are 2 well-linked processes during leukemia development and are controlled by the bone marrow (BM) niche. Extracellular matrix proteins, including laminin, are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown. Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is altered in BM niches in mice with acute myeloid leukemia (AML). So far, the impact of Lama4 on leukemia progression remains unknown. We here report that Lama4 deletion in mice resulted in impaired hematopoiesis regeneration following irradiation-induced stress, which is accompanied by altered BM niche composition and inflammation. Importantly, in a transplantation-induced MLL-AF9 AML mouse model, we demonstrate accelerated AML progression and relapse in Lama4-/- mice. Upon AML exposure, Lama4-/- mesenchymal stem cells (MSCs) exhibited dramatic molecular alterations, including upregulation of inflammatory cytokines that favor AML growth. Lama4-/- MSCs displayed increased antioxidant activities and promoted AML stem cell proliferation and chemoresistance to cytarabine, which was accompanied by increased mitochondrial transfer from the MSCs to AML cells and reduced reactive oxygen species in AML cells in vitro. Similarly, we detected lower levels of reactive oxygen species in AML cells from Lama4-/- mice post-cytarabine treatment. Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates the critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.