title: Notch-directed microenvironment reprogramming in myeloma: a single path to multiple outcomes.
abstract: Multiple myeloma is a deadly hematopoietic malignancy. Despite therapeutic advances such as autologous stem cell transplantation and novel chemotherapeutics, multiple myeloma remains incurable. Multiple myeloma cell localization in the bone marrow and the cross-talk with the bone niche trigger dramatic alterations in the bone marrow microenvironment critical for tumor progression, resistance to therapies and osteolytic bone destruction. It does not surprise that the molecular bases of such fatal interaction are under examination as source of novel potential pharmacological targets. Among these, the Notch family of receptors and ligands has gained growing interest in the recent years because of their early deregulation in multiple myeloma and their ability to affect multiple features of the disease, including tumor cell growth, drug resistance, angiogenesis and bone lesions. This review will explore the evidences of Notch deregulation in multiple myeloma, the state of the art of the currently known roles of its signaling in the fatal interaction between multiple myeloma cells, extracellular matrix and cells in the bone marrow stroma. Finally, we will present recent findings concerning the arguments for or against a therapy addressed to Notch signaling inhibition in the cure of multiple myeloma.
authors.affiliation: Department of Health Science, Università degli Studi di Milano, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colombo
authors.forename: L
authors.initials: L
authors.lastname: Mirandola
authors.forename: N
authors.initials: N
authors.lastname: Platonova
authors.forename: L
authors.initials: L
authors.lastname: Apicella
authors.forename: A
authors.initials: A
authors.lastname: Basile
authors.forename: A J
authors.initials: AJ
authors.lastname: Figueroa
authors.forename: E
authors.initials: E
authors.lastname: Cobos
authors.forename: M
authors.initials: M
authors.lastname: Chiriva-Internati
authors.forename: R
authors.initials: R
authors.lastname: Chiaramonte
mesh_terms: D001854:Bone Marrow Cells / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D018450:Disease Progression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D000072101:Jagged-2 Protein; D008565:Membrane Proteins / Q000502:physiology; D009101:Multiple Myeloma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D018919:Neovascularization, Physiologic; D010014:Osteolysis; D019718:Receptors, CXCR4 / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C527276:CXCR4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C490504:JAG2 protein, human; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D051880:Receptors, Notch