ArticleFrontiers in cell and developmental biology2021
Hematopoietic Cell Kinase (HCK) Is a Player of the Crosstalk Between Hematopoietic Cells and Bone Marrow Niche Through CXCL12/CXCR4 Axis.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- From pumps to networks: ABC transporters in leukemia resistance and microenvironmental adaptation.Medical oncology (Northwood, London, England) · 2026Review
- Synthetic Substrate Discovery for Hck Kinase via Phage Display.Biochemistry · 2026Article
- Article
- Longitudinal localization of leukaemic stem cells between the metaphysis and central marrow governs their behaviour.Nature cell biology · 2026Article
- Macrophage polarization in hematologic cancers: mechanisms and therapeutic strategies.Blood research · 2026Review
- Review
- DCC-2036 inhibits osteosarcoma via targeting HCK and the PI3K/AKT-mTORC1 axis to promote autophagy.World journal of surgical oncology · 2025Article
- β-Carboline derivatives are potent against Acute Myeloid Leukemia in vitro and in vivo.Pharmacological reports : PR · 2024Article
- CD3ζ-Mediated Signaling Protects Retinal Ganglion Cells in Glutamate Excitotoxicity of the Retina.Cells · 2024Article
- Pathological progression of osteoarthritis: a perspective on subchondral bone.Frontiers of medicine · 2024Review
- Understanding the interaction between leukaemia stem cells and their microenvironment to improve therapeutic approaches.British journal of pharmacology · 2024Review
- Knockdown of HCK promotes HREC cell viability and inner blood-retinal barrier integrity by regulating the AMPK signaling pathway.Open life sciences · 2024Article
- Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells.Biomolecules · 2022Review
- PI3K Targeting in Non-solid Cancer.Current topics in microbiology and immunology · 2022Review
- Comprehensive analysis of the HCK gene in myeloid neoplasms: Insights into biological functions, prognosis, and response to antineoplastic agents.Hematology, transfusion and cell therapyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The crosstalk between hematopoietic stem/progenitor cells (HSC), both normal and leukemic, and their neighboring bone marrow (BM) microenvironment (niche) creates a reciprocal dependency, a master regulator of biological process, and chemotherapy resistance. In acute myeloid leukemia (AML), leukemic stem/progenitor cells (LSC) anchored in the protective BM microenvironment, reprogram and transform this niche into a leukemia-supporting and chemoprotective environment. One most important player involved in this crosstalk are CXCL12, produced by the BM mesenchymal stromal cells, and its receptor CXCR4, present onto HSC. The downstream molecular mechanisms involved in CXCL12/CXCR4 axis have many targets, including the Src family members of non-receptor tyrosine kinase (SFK). We herein study the role of one SFK member, the Hematopoietic Cell Kinase (HCK), in CXCL12/CXCR4 pathway and its contribution to the AML pathogenesis. We verified that the inhibition of HCK severely impaired CXCL12-induced migration of leukemic cell lines and CD34 positive cells from AML patients bone marrow, through a disruption of the activation of CXCL12/CXCR4/PI3K/AKT and CXCL12/CXCR4/MAPK/ERK signaling, and by a decreased cytoskeleton dynamic through a lower rate of actin polymerization. We provide new insights into the key role of HCK in conferring a migratory advantage to leukemic cells thought CXCL12/CXCR4 axis. HCK represents an important protein of the main pathway involved in the crosstalk between HSC, and their surrounding milieu. Thus, HCK inhibition could represent a novel approach for the treatment of the acute myeloid leukemia.
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