Abstract
Numerous cell–cell and cell–matrix interactions within the bone marrow microenvironment enable the controlled lifelong self-renewal and progeny of hematopoietic stem and progenitor cells (HSPCs). On the cellular level, this highly mutual interaction is granted by cell adhesion molecules (CAMs) integrating differentiation, proliferation, and pro-survival signals from the surrounding microenvironment to the inner cell. However, cell–cell and cell–matrix interactions are also critically involved during malignant transformation of hematopoietic stem/progenitor cells. It has become increasingly apparent that leukemia-associated gene products, such as activated tyrosine kinases and fusion proteins resulting from chromosomal translocations, directly regulate the activation status of adhesion molecules, thereby directing the leukemic phenotype. These observations imply that interference with adhesion molecule function represents a promising treatment strategy to target pre-leukemic and leukemic lesions within the bone marrow niche. Focusing on myeloid leukemia, we provide a current overview of the mechanisms by which leukemogenic gene products hijack control of cellular adhesion to subsequently disturb normal hematopoiesis and promote leukemia development.
Highlights
We summarize by which leukemogenic gene products control adhesion and migration and discuss the consequences recent findings concerning the mechanisms by which leukemogenic gene products control adhesion of direct cell adhesion molecules (CAMs) regulation on leukemia development
These aberrations trigger and/or survival. This was thethe firstfirst suggestion that mutations in bone trigger leukemic leukemicblast blastcell cellgrowth growth and/or survival. This was suggestion that mutations in bone marrow niche cells contribute to the survival of leukemia patients
Increasing evidence suggests that oncogenes directly regulate the activity of adhesion molecules to control malignant hematopoietic progenitor cell proliferation, self-renewal, survival, and differentiation
Summary
Cellular adhesion plays a vital role in many physiological and pathological processes, including developmental morphogenesis, differentiation, inflammatory responses, angiogenesis, wound healing, tumor progression, and metastasis [1]. Cellular adhesion is mediated by CAMs, which are found in metazoans ranging from sponges to complex mammals. CAMs further modulate intracellular signal transduction, thereby regulating self-renewal, differentiation, and apoptosis. The three conserved CAM domains include an intracellular domain (which interacts with the cytoskeleton), a transmembrane domain, and an extracellular domain. Junctional adhesion mechanisms, which mainly grant intercellular tight junctions in cell assemblies, are distinct from non-junctional adhesion mechanisms, such as integrin- and selectin-mediated adhesion. Cancers 2019, 11, x protein sequences andand structures, CAMs have been cadherin the protein sequences structures, CAMs have beenclassified classifiedinto intofour fourmajor major types: types: the the cadherin superfamily, the the immunoglobulin immunoglobulin superfamily superfamily (IgCAM),.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
